Encyclopedia of Genetics, Rev. Ed.
Field of Study: Genetic engineering and biotechnology
Significance: Implanting genes from one organism into the genome of another enables scientists to study basic genetic mechanisms and inherited diseases and to create plants and animals with traits that are beneficial to humans.
GENOME: the complete genetic material carried by an individual
PLASMID: a circular piece of bacterial DNA that is often used as a vector
TRANSFORMATION: integration of foreign DNA into a cell
TRANSGENE: the foreign gene incorporated into a cell's DNA during
VECTOR: a carrier molecule that introduces foreign genetic materials into
Domestication and selective breeding of animals and plants began before recorded history. In fact, historians propose, the shaping of organisms to fit human needs contributed to the rise of settled, complex culture. Until late in the twentieth century, farmers and scientists could breed novel strains only from closely related species or subspecies because the DNA had to be compatible in order to produce offspring that in turn are fertile.
In the late 1970's and early 1980's, molecular biologists learned how to surpass the limitations of selective breeding. They invented procedures for combining the DNA of species as distantly related as plants and animals. Organisms produced by such means are termed transgenic. This branch of genetic engineering made it possible to design novel organisms for genetic and biochemical research and for medical, agricultural, and ecological innovations. Commercial use of transgenic organisms also created worldwide controversy because of their potential threat to human health and the environment.
Transgenesis is much like gene therapy in that both transform cells for a specific purpose. However, whereas gene therapy targets only certain cells in order to cure a defect in them, transgenesis seeks to produce an entirely modified organism by incorporating the transgene into all the cells of the mature organism and changing the genome. This is done by transforming not only the somatic (body) cells of the host organism but also the germ cells, so that when the organism reproduces, the transgene will pass to the next generation. Transgenes perform their alterations by blocking the function of a host gene, by replacing the host gene with one that codes for a variant protein, or by introducing an additional gene.
In 1978, yeast cells were the first to be transformed by insertion of foreign DNA, followed by mouse cells in 1979. Mouse embryos were transformed in 1980, which later led to the development of a "supermouse" that grew much larger than ordinary mice because it had received the gene for human growth hormone. Most of these transformations came after microinjection of DNA directly into cells. Later, scientists were able to deliver foreign genes into hosts by several other methods: incorporating them into retroviruses and then infecting target cells; electroinfusion, whereby an electric current passed the foreign DNA through the relatively flimsy animal cell wall; biolistics, a means of mechanically shooting a DNA bullet into cells; and conveying the DNA into an ovum aboard sperm. Two methods, developed at first for mice, are particularly successful in growing genetically modified animals after transformation. The first entails injecting transformed embryonic stem cells into a blastocyst (an early spherical form of an embryo). In the second, the DNA is inserted into the pronucleus of a freshly fertilized egg. The blastocyst or egg is then implanted into a foster mother for gestation.
The first complex transgenic animals were intended for genetic research. After disabling a specific gene, scientists could study its effect on the appearance, metabolic processes, and health of the mature animal. By 2003 thousands of genes had been tested. Also, research with mice transformed with human DNA enabled scientists to identify genes associated with breast and prostate cancers, cystic fibrosis, Alzheimer's disease, and severe combined immunodeficiency syndrome (SCIDS). In 2001 the first transgenic primate, a rhesus monkey, was born, potentially supplying a research model genetically much more similar to humans than mice are.
Beginning in the late 1990's, transgenic animals were developed for production of proteins that can be used in pharmaceutical drugs to treat human disease. Accordingly, they have become known as "pharm" animals. Lactating transgenic mice make tissue plasminogen activator in their milk. Similarly, transgenic sheep supply blood coagulation factor IX and alpha1-antitrypsin, transgenic pigs produce human hemoglobin, and transgenic cows make human lactoferrin. Scientists have also developed transgenic pigs that may supply tissue and organs for transplantation into humans without tissue rejection.
Plant cells present greater difficulties for transformation because their cells walls are sturdier than animal cell walls. Microinjection or biolistics are possible but tricky and slow. A breakthrough for plant transgenesis came in 1983, when three separate teams of scientists used plasmids as vectors (carrier molecules) to infect plants with foreign DNA. The achievement came about because of research into plant tumors caused by crown gall disease. The pathogen, the soil bacterium Agrobacterium tumefaciens, caused the disease by ferrying bits of its own DNA into the genome of plants via plasmids, circular bits of extranuclear DNA. Scientists found that they could take the same plasmid, cut out bits of its DNA with enzymes and insert transgenes, and then use the altered plasmids as vectors to transform plants. Subsequently, scientists discovered that liposomes can be vectors. A liposome is a tiny ball of lipids that binds readily to a cell wall, opens a passage, and delivers any DNA that has been put inside it.
A great variety of transgenic plants have been designed for agriculture to produce genetically modified (GM) foods. The first to be marketed was a strain of tomato that ripened slowly so that it gained flavor by staying longer on the vine and remained ripe longer on supermarket shelves. This FlavrSavr tomato was not a commercial success, however. Corn, cotton, soybeans, potatoes, and papayas received a gene from the bacterium Bacillus thuringiensis (Bt) that enables them to make a caterpillar-killing toxin; these are frequently referred to a Bt crops. Other crops have been made resistant to herbicides so that weeds can be easily killed without harming the food plants. Similarly, some transgenic crops tolerate salty or aluminum-rich soil, have less impact on the land because they require less water or tillage, or produce a high yield.
Like transgenic animals, some transgenic crops promise to deliver pharmaceuticals at lower costs and more conveniently than factory-made drugs. GM bananas and potatoes contain vaccines for protection against diarrheal diseases, such as cholera, and hepatitis B. In 2000, scientists reported invention of rice and wheat strains that produce anti-cancer antibodies. Golden rice, a transgenic strain that contains vitamin A, was developed to ward off blindness from vitamin A deficiency, which is a problem in countries that subsist largely on rice. Another strain has elevated iron levels to combat anemia. In a bid to reduce the health risk from smoking, a tobacco company developed a strain free of nicotine.
The Debate over Transgenesis
Transgenic organisms offer great benefits to humankind: deeper understanding of the genetic component in disease and aids in diagnosis; new, cheaper, more easily produced drugs; and crops that could help alleviate the growing hunger in the world. Yet during the 1990's protests against transgenesis began that are as contentious than any since the controversy over the pesticide DDT during the 1960's.
Some opponents object to the very fact that organisms are modified strictly for human benefit. They find such manipulations of life's essential code blasphemous and arrogant, or at the very least unethical and reckless. Furthermore, animal rights groups regard the production of transgenic pharm and research animals cruel and in violation of the natural rights of other species.
The greater portion of opponents, however, are concerned with specific dangers that transgenic organism may pose. Many consumers, most noticeably those in Europe, worry that GM foods contain hidden health risks. After transgenes were found to escape from crops and become part of wild plants, environmentalists proposed that there could be unforeseen and harmful ecological consequences, especially in the destruction of natural species and reduction of biodiversity.
Even those who welcome the creation of transgenic animals and plants are concerned about the legal and social effects. Principally, because biotechnology corporations can patent transgenic organisms, they potentially have great influence on agribusiness, perhaps to the detriment of small farmers and consumers.
Roger SmithSee Also
Antibodies; Biopesticides; Biopharmaceuticals; Genetic Engineering; Genetic Engineering: Agricultural Applications; Genetic Engineering: Medical Applications; Genetic Engineering: Risks; Genetic Engineering: Social and Ethical Issues; Genetically Modified (GM) Foods; Genomics; Human Growth Hormone; Hybridization and Introgression; Knockout Genetics and Knockout Mice; Lateral Gene Transfer; Model Organism: Drosophila melanogaster; Model Organism: Mus musculus; Model Organism: Xenopus laevis; Molecular Genetics; Viroids and Virusoids.
Brown, Kathryn, Karen Hopkin, and Sasha Nemecek. "GM Foods: Are They Safe?" Scientific American 284, no. 4 (2001): 52-57. Describes the risks and benefits in growing genetically modified foods and human consumption of them. Accompanied by graphics and tables that summarize and clarify technical matters.
Lurquin, Paul F. The Green Phoenix: A History of Genetically Modified Plants. New York: Columbia University Press, 2001. Written by a pioneer in the field of transgenic plants, this technically detailed but readable book requires a basic familiarity with microbiology and genetics. The author discusses the ecological and ethical controversies with insight and balance.
Nicholl, Desmond S. T. An Introduction to Genetic Engineering. 2d ed. Cambridge, England: Cambridge University Press, 2002. A thorough, lucidly structured survey of the techniques and applications of genetic engineering. One chapter is devoted transgenic plants and animals.
Velander, William, et al. "Transgenic Livestock as Drug Factories." Scientific American 276 (January, 1997). Explains how genetic engineering methods have resulted in the production of "pharm" animals whose milk contains large amounts of medicinal proteins.
Winston, Mark L. Travels in the Genetically Modified Zone. Cambridge, Mass.: Harvard University Press, 2002. A popular account of the agribusiness, government oversight, and science of genetically modified plants and animals. The science is explained cursorily for general readers.
Web Sites of Interest
Oak Ridge National Laboratory. Transgenic and Targeted Mutant Animal Database. http://www.ornl.gov/TechResources/Trans/hmepg.html. A searchable professional database about lines of genetically modified animals, methods used to create them and descriptions of the modified DNA, the expression of transgenes, and how transgenes are named.
TBASE: The Transgenic/Targeted Mutation Database, Jackson Laboratory, Bar Harbor, Maine. http://tbase.jax.org. Database of information about transgenic animals generated worldwide, searchable by species, technique, DNA construct, phenotype, laboratory. Features the "Knockout Model of the Month"--a discussion of new animal models--and a glossary.
Transgenic Crops: An Introduction and Resource Guide. http://www.colostate.edu/programs/lifesciences/transgeniccrops. This richly illustrated site provides information about the history of plant breeding, the making of transgenic plants, government regulations, and risks and concerns. Also available in Spanish.
University of Michigan. Transgenic Animal Model Core. http://www.med.umich.edu/tamc. A professional Web site for researchers seeking a host animal to test transgenes. However, it contains much useful general information about transgenics (especially transgenic rats), vectors, and laboratory procedures. With links and a photo gallery.
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