Genetic Engineering
Genetic engineering is the altering of the genetic material of living cells in order to make them capable of producing new substances or performing new functions, like getting a micro-organism to produce human insulin or a sheep to produce a human blood-clotting protein in its milk. The technique became possible during the 1950s when scientists discovered the structure of deoxyribonucleic acid (DNA) molecules and how DNA stores and transmit genetic information. Largely as the result of the pioneering work of James Watson (1928-) and Francis Crick (1916-), scientists found that the sequence of nitrogen bases that make up any specific DNA molecule codes for the manufacture of specific chemical compounds. That sequence acts, therefore, as an "instruction manual" that directs all cell functions. Certain practical consequences of that discovery became almost immediately apparent. Suppose that the base sequence T-G-G-C-T-A-C-T on a DNA molecule carries the instruction "make insulin." (The actual sequence for such a message would in reality be very much longer.) DNA in the cells of the islets of Langerhans in the pancreas would normally contain that base sequence since the islets are the region in which insulin is produced in mammals. But that base sequence carries the same message no matter where it is found. If a way could be found to insert the base sequence into the DNA of bacteria, for example, then those bacteria would be capable of manufacturing insulin.
Although the concept of gene transfer is relatively simple, its actual execution presents a number of difficult technical challenges. In 1973, American biochemist Paul Berg, often referred to as the father of genetic engineering, developed a method for joining the DNA from two different organisms, a monkey virus known as SV40 and a second virus known as lambda phage. The accomplishment was significant, but Berg's method was slow and laborious. A turning point came later the same year when Stanley Cohn at Stanford and Hubert Boyer at the University of California at San Francisco discovered an enzyme that greatly increased the efficiency of the Berg process. The technique of gene transfer developed by Berg, Boyer, and Cohen is fundamentally that used in most animal genetic engineering today. This technique requires three elements: the gene to be transferred, a host cell in which the gene is to be inserted, and a vector for transferring the gene to the body. Suppose, for example, that one wishes to insert the insulin gene into a bacterial cell. The first step is to obtain a copy of the insulin gene. This copy can be obtained from a natural source (like DNA in islets of Langerhans cells), or it can be manufactured artificially in the laboratory. The second step is to insert the insulin gene into the vector. Viruses, liposomes (hollow spheres of fat molecules formed in solution), and plasmids (circular forms of DNA) are common vectors. Scientists have discovered enzymes that can "recognize" certain base sequences in a DNA molecule and cut the molecule open at these locations. In this case, the plasmid vector can, therefore, be cleaved at almost any point chosen by the scientist. Once the plasmid has been cleaved, it is mixed with the insulin gene and another enzyme that has the ability to glue the DNA molecule back together. In this case, however, the insulin gene attaches itself to the plasmid before the plasmid is re-closed. The hybrid plasmid now contains the gene whose product (insulin) is desired. It can be inserted into the host cell where it begins to function as all bacterial genes function. In this case, however, in addition to normal bacterial functions, the host cell is also producing insulin as directed by the inserted gene. This method is sometimes referred to as gene splicing. Since genes from two different sources have been combined with each other, the technique is also called recombinant DNA (rDNA) research.
The possible applications of genetic engineering are nearly limitless. For example, rDNA methods now make it possible to produce a number of natural products that were previously available in only very limited amounts. Until the 1980s, for example, the only supply of insulin available to diabetics was animals slaughtered for meat or other purposes. That supply was never adequate to treat all diabetics at moderate cost. In 1982, however, the United States Food and Drug Administration approved insulin produced by genetically altered organisms, the first such product to become available. Since 1982, a number of additional products, including human growth hormone, alpha interferon, interleukin-2, erythropoietin, tumor necrosis factor, and tissue plasminogen activator have been produced by rDNA techniques. In addition to the production of insulin, this technique has been used to create recombinant factor VIII for the treatment of hemophilia, a hereditary blood defect that inhibits blood clotting and makes it difficult for the body to naturally control bleeding. This genetically engineered blood factor protein can help induce clotting. Available since 1993, factor VIII can, for example, be produced in hamster cell lines using Bovine serum proteins. It is considered safer than similar blood-derived factors which have the potential to pass on blood viruses, such as AIDS or hepatitis. Several other similar blood factor products are under development.
The potential commercial value of genetically engineered products was not lost on entrepreneurs in the 1970s. In many cases, the founders of the first genetic engineering firms were scientists themselves, often those involved in basic research in the field. Boyer, for example, joined with venture capitalist Robert Swanson in 1976 to form Genentech (Genetic Engineering Technology). Other early firms like Cetus, Biogen, and Genex were formed similarly through the collaboration of scientists and business people. The structure of genetic engineering (or, more generally, biotechnology) firms has been a source of controversy, with concerns about individual scientists making a profit by opening their own companies that are based on research carried out at public universities and paid for with federal funds. By the early 1990s, working relationships had, in many cases, been formalized among universities, individual researchers, and the corporations they establish. But not everyone is satisfied that the ethical issues involved in such arrangements are settled.
One of the most exciting potential applications of genetic engineering involves the treatment of genetic disorders. Medical scientists now know of more 3,000 disorders that arise because of errors in an individual's DNA and are continuously finding new links among genes and diseases. Conditions such as sickle-cell anemia, Tay-Sachs disease, Duchenne muscular dystrophy, Huntington's chorea, cystic fibrosis, and Lesch-Nyhan syndrome are the result of the loss, mistaken insertion, or change of a single nitrogen base in a DNA molecule. Genetic engineering makes it possible for scientists to provide individuals who lack a certain gene with correct copies of that gene. If and when that correct gene begins to function, the genetic disorder may be cured. This procedure is known as human gene therapy. The first approved trials of gene therapy with human patients were begun in 1989. One of the most promising sets of experiments involved a condition known as severe combined immune deficiency (SCID) or ADA deficiency. Children born with this disorder have no immune system because of the lack of a single gene. In 1990, a research team at the National Institutes of Health led by W. French Anderson attempted gene therapy with a four-year old patient with SCID. The patient received about a billion cells containing a genetically engineered copy of the ADA gene that the child's body lacked. Human gene therapy is the source of great controversy among scientists and non-scientists alike. Few individuals would say that the technique should never be used, especially for battling life threatening diseases, like AIDS and cancer. But many critics worry about where gene therapy might lead, such as genetically engineered humans.
Genetic engineering also promises a revolution in agriculture. Recombinant DNA techniques make it possible to produce plants that are resistant to herbicides, that will survive freezing temperatures, that will take longer to ripen, that will convert atmospheric nitrogen to a form they can use, that will manufacture their own resistance to pests, and so on. Scientists have tested a multitude of plants engineered to have special properties such as these. In 1994, a tomato was the first genetically engineered food to appear in American supermarkets. The genetically engineered tomato was created with an "antisense" gene that allows the tomato to ripen on the vine but remain firm for shipping. As with every other aspect of genetic engineering, however, these advances have been controversial. The development of herbicide-resistant plants, for example, only means that farmers will use still larger quantities of herbicides, critics say, not an especially desirable trend. How sure can we be, others ask, about the potential risk to the environment posed by the introduction of "unnatural" engineered plants? For example, in the case of the tomato, some people are concerned genes from the plant could spread into soil bacteria and then infect humans or animals. Many other applications of genetic engineering have already been developed or are likely to be realized in the future. In every case, however, the glowing promises of each new technique is somewhat tempered by the social, economic and ethical questions it raises.
Genetically engineered clones (exact genetic copies of an individual), for example, became a major issue in 1997 when scientists from Scotland announced that they had successfully created the first clone of an adult mammal. The genes used to clone Dolly the sheep came from the frozen mammary tissue of a six-year-old dead sheep. The cloning was accomplished by taking the cell nucleus from a Finn Dorset sheep and then substituting it with the egg from the dead Poll Dorset sheep. The nucleus with the egg was then implanted into a third Scottish Blackface sheep. Because of the three different breeds used, the researchers had ready evidence that Dolly was truly a clone. While Dolly was a major advance scientifically, she became more famous among the public because of the ethical furor that has surrounded her "creation." Using genetic engineering to clone humans could be abused to create certain "types" of people, bringing forth the specter of humans as objects instead of individuals. Both the United States and Great Britain have banned human cloning. Still, the cloning of animals has many potential benefits, including raising animals that could be genetically engineered to produce more meat or, perhaps, to produce a human gene protein that could then be used in gene therapy.
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Genetic Engineering from World of Invention. ©2005-2006 Thomson Gale, a part of the Thomson Corporation. All rights reserved.
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