Transgenics

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Transgenics

The term transgenics refers to the process of transferring genetic information from one organism to another. By introducing new genetic material into a cell or individual , a transgenic organism is created that has new characteristics it did not have before. The genes transferred from one organism or cell to another are called transgenes. The development of biotechnological techniques has led to the creation of transgenic bacteria , plants, and animals that have great advantages over their natural counterparts and sometimes act as living machines to create therapeutics for the treatment of disease . Despite the advantages of transgenics, some people have great concern regarding the use of transgenic plants as food, and with the possibility of transgenic organisms escaping into the environment where they may upset ecosystem balance.

All of the cells of every living thing on Earth contain DNA (deoxyribonucleic acid). DNA is a complex and long molecule composed of a sequence of smaller molecules, called nucleotides, linked together. Nucleotides are nitrogen-containing molecules, called bases that are combined with sugar and phosphate. There are four different kinds of nucleotides in DNA. Each nucleotide has a unique base component. The sequence of nucleotides, and therefore of bases, within an organism's DNA is unique. In other words, no two organisms have exactly the same sequence of nucleotides in their DNA, even if they belong to the same species or are related. DNA holds within its nucleotide sequence information that directs the activities of the cell. Groups, or sets of nucleotide sequences that instruct a single function are called genes.

Much of the genetic material, or DNA, of organisms is coiled into compact forms called chromosomes. Chromosomes are highly organized compilations of DNA and protein that make the long molecules of DNA more manageable during cell division . In many organisms, including human beings, chromosomes are found within the nucleus of a cell. The nucleus is the central compartment of the cell that houses genetic information and acts as a control center for the cell. In other organisms, such as bacteria, DNA is not found within a nucleus. Instead, the DNA (usually in the form of a circular chromosome ) is free within the cell. Additionally, many cells have extrachromosomal DNA that is not found within chromosomes. The mitochondria of cells, and the chloroplasts of plant cells have extrachromosomal DNA that help direct the activities of these organelles independent from the activities of the nucleus where the chromosomes are found. Plasmids are circular pieces of extrachromosomal DNA found in bacteria that are extensively used in transgenics.

DNA, whether in chromosomes or in extrachromosomal molecules, uses the same code to direct cell activities. The genetic code is the sequence of nucleotides in genes that is defined by sets of three nucleotides. The genetic code itself is universal, meaning it is interpreted the same way in all living things. Therefore, all cells use the same code to store information in DNA, but have different amounts and kinds of information. The entire set of DNA found within a cell (and all of the identical cells of a multicellular organism) is called the genome of that cell or organism.

The DNA of chromosomes within the cellular genome is responsible for the production of proteins . Proteins have many varied and important functions, and in fact help determine the major characteristics of cells and whole organisms. As enzymes, proteins carry out thousands of kinds of chemical reactions that make life possible. Proteins also act as cell receptors and signal molecules, which enable cells to communicate with one another, to coordinate growth and other activities important for wound healing and development. Thus, many of the vital activities and characteristics that define a cell are really the result of the proteins that are present. The proteins, in turn, are determined by the genome of the organism.

Because the genetic code is universal (same for all known organisms), and because genes determine characteristics of organisms, the characteristics of one kind of organism can be transferred to another. If genes from an insect, for example, are placed into a plant in such a way that they are functional, the plant will gain characteristics of the insect. The insect's DNA provides information on how to make insect proteins within the plant because the genetic code is interpreted in the same way. That is, the insect genes give new characteristics to the plant. This very process has already been performed with firefly genes and tobacco plants. Firefly genes were transferred into tobacco plants, which created new tobacco plants that could glow in the dark. This amazing artificial genetic mixing, called recombinant biotechnology , is the crux of transgenics. The organisms that are created from mixing genes from different sources are transgenic. The glow-in-the-dark tobacco plants in the previous example, then, are transgenic tobacco plants.

DNA transfer

One of the major obstacles in the creation of transgenic organisms is the problem of physically transferring DNA from one organism or cell into another. It was observed early on that bacteria resistant to antibiotics transferred the resistance characteristic to other nearby bacterial cells that were not previously resistant. It was eventually discovered that the resistant bacterial cells were actually exchanging plasmid DNA carrying resistance genes. The plasmids traveled between resistant and susceptible cells. In this way, susceptible bacterial cells were transformed into resistant cells.

The permanent modification of a genome by the external application of DNA from a cell of a different genotype is called transformation (in bacteria) or transfection (in plant or animal cells). Transformed cells can pass on the new characteristics to new cells when they reproduce because copies of the foreign transgenes are replicated during cell division. Transformation can be either naturally occurring or the result of transgenic technology. Scientists mimic the natural uptake of plasmids by bacterial cells for use in creating transgenic cells. Chemical, physical, and biological methods are used to introduce DNA into the cells.

Cells can be pre-treated with chemicals in order to more willingly take-up genetically engineered plasmids. Also DNA can be mixed with chemicals such as liposomes to introduce transgenes into cells. Liposomes are microscopic spheres filled with DNA that fuse to cells. When liposomes merge with host cells, they deliver the transgenes to the new cell. Liposomes are composed of lipids very similar to the lipids that make up cell membranes, which gives them the ability to fuse with cells.

Physical methods for DNA transfer include electroporation (bacterial and animal cells), microinjection of DNA and gene gun. Electroporation is a process where cells are induced by an electric current to take up pieces of foreign DNA. DNA can also be introduced into cells by microinjection using microscopic needles. Plant tissues are difficult to penetrate due to the presence of a cell wall so a gene gun shooting pellets covered with DNA is used to transfer DNA to plants.

Biological methods used in gene transfer include viruses, fungi, and bacteria that have been genetically modified. Viruses that infect bacterial cells are used to inject the foreign pieces of DNA.

Use of transgenics

The use of transgenics depends on the type of organism being modified. Transgenic bacteria are used to produce antibiotics on an industrial scale, new protein drugs and to metabolize petroleum products, or plastics for cleaning up the environment.

By creating transgenic plants, food crops have enhanced productivity and quality. Transgenic corn, wheat , and soy with herbicide resistance, for example, are able to grow in areas treated with herbicide that kills weeds. In 2000, a list of 52 transgenic plants were approved for field trials in the United States alone, and plants included fruits (cranberries or papayas), vegetables (potatoes or carrots), industrial plants (cotton or wheat), and ornamental plants. Although the majority of the improvements remain confidential, it is known that scientists try to improve sugar metabolism , resistance to drought or cold, and yields by modifying photosynthetic abilities of plants. Additionally, tests are on the way to establish feasibility of edible vaccines using lettuce, corn, tomatoes and potatoes. More recent studies suggests that plants can also be used to produce other pharmaceuticals, for example growth hormone, erythropoietin or interferons , however, the amounts produced are too low to be of commercial value as yet.

Transgenic animals are useful in basic research for determining gene function. They are also important for creating disease models and in searching for therapeutics. Recent developments in transgenic technology allow researchers to study the effects of gene deletion, over-expression, and inhibition in specific tissues. Such studies can allow identification of the drug targets in individual tissues or evaluate other gene therapy only in tissues of interest. Commercially transgenic animals are used for production of monoclonal antibodies, pharmaceuticals, xenotransplantation and meat production. New areas in large animal transgenics is expression of a bacterial enzyme phytase in pigs allowing reduction of phosphorus excreted into the environment. In general, by using transgenics scientists can accomplish the results similar as with selective breeding.

Despite their incredible utility, there are concerns regarding transgenics. The Human Genome Project is a large collaborative effort among scientists worldwide that announced the determination of the sequence of the entire human genome in 2000. In doing this, the creation of transgenic humans could become more of a reality, which could lead to serious ramifications. Also, transgenic plants used as genetically modified food is a topic of debate. For a variety of reasons, not all scientifically based, some people argue that transgenic food is a consumer safety issue because not all of the effects of transgenic foods have been fully explored. Also of great debate are the environmental protection issues as the transgenic plants can cross-pollinate with wild varieties, which in turn can lead to unforeseen consequences.

Resources

books

Houdebine, Louis M. Transgenic Animals. Harwood Academic Publishing, 1997.

Rissler, Jane, and Margaret Mellon. The Ecological Risks of Engineered Crops. MIT Press, 1996.

Ticciati, L., and R. Ticciati. Genetically Engineered Foods: Are They Safe? You Decide. Keats Publishing, 1998.

periodicals

Daniell, Henry, Stephen J. Streatfield, and Keith Wycoff. "Medical Molecular Farming: Production of Antibodies, Biopharmaceuticals and Edible Vaccines in Plants." Trends in Plant Science (May 2001): 219–226.

Golovan, Serguei P., et al. "Pigs Expressing Salivary Phytase Produce Low-phosphorus Manure." Nature Biotechnology (August 2001): 741–45.

"Hunting Down Genes that Say 'No' to Disease." Business Week (December 13, 1993): 113.

Terry Watkins

KEY TERMS

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Electroporation: —The induction of transient pores in the plasmalemma by pulses of high voltage electricity, in order to incorporate transgenes from an external source.
Genome: —All of the genetic information for a cell or organism.
Liposomes: —Lipid bubbles used to deliver transgenes to host cells. Liposomes fuse with the lipids of cell membranes, passing transgenes to the inside of host cells in the process.
Photosynthesis: —The process in which plants combine water and carbon dioxide to build carbohydrates using light energy.
Plasmids: —Circular pieces of extrachromosomal DNA in bacteria that are engineered and used by scientists to hold transgenes.
Transfection: —The transgenic infection of host cells using viruses that infect bacterial cells.
Transgenes: —Genes transferred from one organism to another in transgenic experiments. Transgenes are often engineered by scientists to possess certain desirable characteristics.
Transgenics: —The process of transferring genetic material from one organism to another, or one cell to another.
Xenotransplantation: —Transplantation of tissue or an organ from one species to another, for example from pig to human.