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Ward's World+McGraw Hill Biotechnology_2

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Biotechnology (continued) Interferons are also being tested for their use in the manage- ment of specific diseases. They show some promise in treat- ing bovine shipping fever (a complex of respiratory infections manifested during the crowded conditions experienced by cattle when shipped). Recombinant produced bovine growth hormone has been shown to be effective in increasing the production of milk in cows and in reducing the ratio of fat to lean meat in beef cattle. However, its use has been the subject of much debate. Animals may be transformed to carry genes from other spe- cies, including humans, and are being used to produce valu- able drugs. This technology has been termed biopharming. For example, goats are being used to produce tissue plasminogen activator, which has been effective in dissolving blood clots. Transgenic animals have been produced that carry the acquired immune deficiency syndrome (AIDS) virus, providing a practical cost-effective experimental model system to test control mea- sures for the disease, which infects only primates in nature. Plant science Plant scientists have been amazed at the ease with which plants can be transformed to enable them to express foreign genes. This field has developed very rapidly since the first transformation of a plant was reported in 1982, and a number of transformation procedures are available. Most widely used as a transformation vector is the plasmid derived from the plant pathogenic bacterium Agrobacterium tumefaciens (Fig. 3). An- other method involves shooting DNA-coated tungsten (or gold) particles into cells. Controlling genetic elements have been identified that allow for the insertion of genes into specific tis- sues or plant organs. For example, nucleic acid sequences may be targeted to the pollen grain to specifically inactivate genes involved in producing pollen, thereby allowing for the produc- tion of sterile male plants. Such a technique will be very useful in the commercial production of hybrid seeds of crop species. Coupled with these transformation procedures has been the development of tissue culture techniques to enable the trans- formed cells to be regenerated into whole plants (termed toti- potency). Many plant species have been regenerated, thereby facilitating the transfer of useful genes to the most important crops (rice, maize, wheat, and potatoes). Cultures of plant cells, roots, and tissues are used to produce secondary plant prod- ucts, such as the anticancer drug paclitaxel. Medicine Genetic engineering has enabled the large-scale production of proteins that have great potential for treatment of heart at- tacks. Most promising of these new drugs is tissue plasminogen activator, which has been shown to be effective in dissolving blood clots. Active tissue plasminogen activator, a very minor constituent of human blood vessels and some other tissues, may now be produced by recombinant technology in trans- formed tissue culture cells or in the filamentous fungus Asper- gillus nidulans. Another substance produced by recombinant technology that has been tested for treatment of heart attacks is urokinase. Many human gene products, produced with genetic engi- neering technology, are being investigated for their potential use as commercial drugs. Cloned human growth hormone is being used for the treatment of childhood dwarfism. Epidermal growth factor is a protein that causes the replication of epider- mal cells and has applications to wound healing. Interleukins produced by blood cells are being tested for treatment of specific cancers. Granulocyte macrophage colony–stimulating factor is being tested as a treatment for ovarian cancer. Recombinant technology has been employed to produce vaccines from subunits of viruses, so the use of either live or inactivated viruses as immunizing agents is avoided. Con- ventional vaccines are sometimes infectious themselves; in addition, most require refrigeration, which poses a problem in tropical countries. Poliovirus vaccines involving attenuated live virus are a source of the perpetuation of the disease due to rare mutations of the virus to virulence. Recombinant technology is being used to modify the viral genome to prevent reversion. Other viruses being investigated are hepatitis B and herpes simplex, where surface antigens are being produced in yeast cells. Malaria, one of the most important parasitic diseases of humans, is another case in which biotechnology is being ap- plied to produce a vaccine. Proteins from the causal organism, Plasmodium, are poorly immunogenic. To enhance immu- nogenicity, they are transferred to the attenuated bacterium Salmonella typhimurium, which is then used as an immunizing agent. Another strategy has been to fuse the gene for the im- munological determinant to that of a hepatitis B virus protein, to express the fusion protein in yeast, and to use that chimeric protein as a vaccine. + ward ' s science

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