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Genetic Engineering

Genetic engineering is the alteration of genetic material with a view to producing new substances or creating new functions. The technique became possible in the 1950s, when scientists discovered the structure of DNA molecules and learned how these molecules store and transmit genetic information. Largely as a result of the pioneering work of James Watson and Francis Crick, scientists were able to discover the sequence of nitrogen bases that constitute the particular DNA molecule codes for the manufacture of particular chemical compounds. This is the sequence that acts as an "instruction manual" for all cell functions. Certain practical consequences of that discovery were 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 much longer). The 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. It should be noted, however, that the base sequence carries the same message no matter where it is found. If a way could be found to insert that 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 considerable technical obstacles. The first person to surmount these obstacles was the American biochemist Paul Berg, often referred to as the "father of genetic engineering." In 1973, Berg developed a method for joining the DNA from two different organisms: a monkey virus known as SV40 and a virus known as lambda phage. The accomplishment was extraordinary; however, scientists realized that Berg's method was too laborious. A turning point in genetic engineering came later that year, when Stanley Cohen at Stanford and Hubert Boyer at the University of California at San Francisco discovered an enzyme that greatly increased the efficiency of the Berg procedure. The gene transfer technique developed by Berg, Boyer, and Cohen forms the basis of much of contemporary genetic engineering.

This technique requires three elements: the gene to be transferred, a host cell in which the gene is to be inserted, and a vector to effect the transfer. Suppose, for example, that one wishes to insert the insulin in a bacterial cell. The first step is to obtain a copy of the insulin gene. This copy can be obtained from a natural sources (from the DNA in islets of Langerhans cells, for example), or it can be manufactured in a laboratory. The second step is to insert the insulin gene into the vector. The most common vector is a circular form of DNA known as a plasmid. Scientists have discovered enzymes that can "recognize" certain base sequences in a DNA molecule and cut the molecule open at these locations. In fact, the plasmid vector can 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 molecules back together. In this particular 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 a bacterial gene. In this case, however, in addition to normal bacterial functions, the host cell is also producing insulin, as directed by the inserted gene. Because of the nature of the procedure, this method is sometimes referred to as gene splicing; and since the genes have come 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 virtually limitless. For example, rDNA methods now enable scientists to produce a number of products that were previously available only in limited quantities. Until the 1980s, for example, the only source of insulin available to diabetics was found in animals slaughtered for meat and other purposes, and the supply was never high enough to provide a sufficient amount of affordable insulin for diabetics. In 1982, however, the U.S. 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, factor VIII, erythropoietin, tumor necrosis factor, and tissue plasminogen activator have been produced by rDNA techniques.

The commercial potential of genetically products was not lost on entrepreneurs in the 1970s. A few individuals believed, furthermore, that the impact of rDNA on American technology would be comparable to that of computers in the 1950s. In many cases, the first genetic engineering firms were founded by scientists involved in fundamental research. Boyer, for example, joined the venture capitalist Robert Swanson in 1976 to form Genetech (Genetic Engineering Technology). Other early firms like Cetus, Biogen, and Genex were formed similarly through the collaboration of scientists and businesspeople.

The structure of genetic engineering (biotechnology) firms has, in fact, long been a source of controversy. Many have questioned the scientists' right to make a personal profit by running companies which benefit from research that had been carried out at publicly-funded universities.

The early 1990s saw the creation of formalized working relations between universities, individual researchers, and the corporations founded by these individuals. However, despite these arrangements, many ethical issues remain unresolved.

One of the most exciting potential applications of genetic engineering involves the treatment of genetic disorders. Medical scientists know of about 3,000 disorders that arise because of errors in individuals DNA. Conditions such as sickle-cell anemia, Tay-Sachs disease, Duchenne muscular dystrophy, Huntington's chorea, cystic fibrosis, and Lesch-Nyhan syndrome result from the mistaken insertion, omission, or change of a single nitrogen base in a DNA molecule. Genetic engineering enables scientists to provide individuals lacking a particular gene with correct copies of that gene. If and when the correct gene begins functioning, the genetic disorder may be cured. This procedure is known as human gene therapy (HGT).

The first approved trials of HGT with human patients began in the 1980s. One of the most promising sets of experiments involved a condition known as severe combined immune deficiency (SCID). In 1990, a research team at the National Institutes of Health (NIH) led by W. French Anderson attempted HGT on a four-year-old SCID patient, whose condition was associated with the absence of the enzyme adenosine deaminase (ADA). The patient received about a billion cells containing a genetically engineered copy of the ADA gene that his body lacked. Another instance of HGT was a procedure, approved in 1993 by NIH, to introduce normal genes into the airways of cystic fibrosis patients.

Human gene therapy is the source of great controversy among scientist and non-scientists alike. Few individuals maintain that the HGT should not be used. If we could wipe out sickle-cell anemia, most agree, we should certainly make the effort. But HGT raises other concerns. If scientists can cure genetic disorders, they can also design individuals in accordance with the cultural and intellectual fashions of the day. Will humans know when to say "enough" to the changes that can be made with HGT?

Genetic engineering also promises a revolution in agriculture. Recombinant DNA techniques enable scientists to produce plants that are resistant to herbicides and freezing temperatures, that will take longer to ripen, that will convert atmospheric nitrogen to a form they can use, that will manufacture a resistance to pests, and so on. By 1988, scientists had tested more than two dozen kinds of plants engineered to have special properties such as these. As with other aspects of genetic engineering, however, these advances have been controversial. The development of herbicide-resistant plants means that farmers will use still larger quantities of herbicides—not a particularly desirable trend, according to critics. How sure can we be, others ask, about the risk to the environment posed by the introduction of "unnatural," engineered plants?

Many other applications of genetic engineering have already been developed or are likely to be realized in the future.



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