Encyclopedia of 20th Century Technology

(Note: Sample material is taken from uncorrected proofs. Changes may be made prior to publication.)

Genetic Engineering, Applications

For centuries, if not millennia, techniques have been employed to alter the genetic characteristics of animals and plants to enhance specifically desired traits. In a great many cases, breeds with which we are most familiar bear little resemblance to the wild varieties from which they are derived. Canine breeds, for instance, have been selectively tailored to changing aesthetic tastes over many years, altering their appearance, behavior and temperament. Many of the species used in farming reflect long term alterations to enhance meat, milk, and fleece yields. Likewise, in the case of agricultural varieties, hybridization and selective breeding have resulted in crops that are adapted to specific production conditions and regional demands.

Genetic engineering differs from these traditional methods of plant and animal breeding in some very important respects. First, genes from one organism can be extracted and recombined with those of another (using recombinant DNA, or rDNA, technology) without either organism having to be of the same species. Second, removing the requirement for species reproductive compatibility, new genetic combinations can be produced in a much more highly accelerated way than before. Since the development of the first rDNA organism by Stanley Cohen and Herbert Boyer in 1973, a number of techniques have been found to produce highly novel products derived from transgenic plants and animals.

At the same time, there has been an ongoing and ferocious political debate over the environmental and health risks to humans of genetically altered species. The rise of genetic engineering may be characterized by developments during the last three decades of the 20th century and will be presented accordingly.

1970 to 1979
The term genetic engineering was probably first coined by Edward L. Tatum during his 1963 Nobel Prize acceptance speech, but it was not until the following decade that many of the potential applications of gene transfer became more apparent to the emerging field of molecular biology. However, the period was witness to a clash between the new molecular biologists who were pioneering the techniques of genetic engineering and their more industrially related colleagues in microbiology. Whereas the microbiologists, with their roots in the fermentation industries, were more prepared to recognize the potential of genetic engineering, molecular biologists were initially much more concerned with the threats of environmental risk.

As a consequence of a letter to Science and Nature in 1974, known as the Berg letter after its first signatory Paul Berg, molecular biologists instigated a voluntary moratorium on gene transfer work until such time as the community was satisfied that necessary safety measures and procedures had been put in place. Two further key events were instrumental in moving the field forward. The first was the Asilomar Conference in February 1975, which addressed safety measures and, to a lesser extent, prospects for future applications. The second was the publication in 1996 of the first guidelines for gene transfer research released by the US National Institutes for Health, which effectively lifted the moratorium. In 1977, Genentech, Inc., reported the manufacture of the human hormone somatostatin in bacteria genetically engineered to contain a synthetic gene that produced a human protein. This step is widely considered to represent the opening moments of modern biotechnology production.

1980 to 1989
The early 1980s is the first period in which large-scale investments were made in the biotechnology industry against the anticipation of huge profits to follow. Indeed, the first biotechnology stocks to be floated on the markets in the 1980s rose in value far more rapidly than had any other sector up to that time. In 1980 the US Supreme Court allowed patent protection for a genetically modified "oil-eating" bacterium, providing powerful financial incentives for biotechnology companies to expand research. The year 1980 also saw the introduction of the polymerase chain reaction (PCR) technique, through which DNA sequences are multiplied many times in vitro, that became the foundation of much of the work to follow. In 1981 a team at Ohio University produced the first transgenic animals, mice in this case. Shortly afterward, Harvard University released details of studies in which mice were engineered to carry a human gene that increased susceptibility to a form of human cancer. The "OncoMouse," as it became known, could be used to test the carcinogenicity of different compounds and as a model for developing cures for cancer. The OncoMouse, for which Harvard filed a patent in 1984, focused much of the ensuing debate on the future health implications of genetic engineering. By 1983, the first patents had been granted on genetically engineered plants (actually only for the use of an antibiotic resistance "marker gene", that allowed researchers to select transformed plants by their ability to survive exposure to an otherwise lethal dose of an antibiotic). In 1985 the first US field trials of genetically engineered crops (tomatoes with a gene for insect resistance and tobacco plants with herbicide resistance) took place, and in 1986 genetically engineered tobacco plants, modified with addition of a gene from the bacterium Bacillus thuringiensis (Bt) to produce a insecticidal toxin, making the hybrid resistant to the European corn borer and other pests, underwent field trials in the US and France.

1990 to 2000
The 1990s saw considerable growth in a wide range and variety of biotechnological applications, though without necessarily fulfilling the huge expectations evident in the early 1980s. In respect to animal biotechnology products, a number of events can be seen to have defined the decade.

Sizeable resources were directed at the production of proteins and drug compounds in transgenic animals, resulting in over 50 varieties of genetically modified (GM) bioreactors. These methods had a number of advantages over traditional cell culture production including higher production volumes, particularly in respect to those proteins (such as human albumin) that cannot be produced in a sufficient volume using other available techniques. On a considerably smaller scale, research in the 1990s also focused on the production of transgenic animals as sources of transplant tissues and organs. However, the decade closed with little progress seen in either reducing tissue rejection or overcoming anxieties about transpecies disease.

By far the largest research activity was within the field of plant biotechnology. For instance, genetically modified herbicide-tolerant (GMHT) crops were intended to enable varieties to withstand chemical treatments that would normally damage them. The same concept was applied to the production of insect and virus-resistant plant varieties, in addition to altering the way fruits ripen so that they can withstand increased storage and travel stresses. In 1994, the Flavr Savr tomato, designed to delay ripening and resist rotting, became the first whole genetically engineered food to be approved for sale in the United States (China commercialized virus-resistant tobacco plants in the early 1990s). In 2000, a rice variety was genetically engineered to contain a gene which increases the vitamin A content of the grains. Similar improvements could be made to the composition of other important food staples. Another widespread application of genetic engineering prevented plants from pollinating in order to limit the chances of cross-fertilization with other species. A more controversial aspect of genetically modified plants was their inability to reproduce so that growers would be unable to collect seeds for replanting, and thus forced to purchase seed from the supplier each season.

The 1990s were also characterized by what became known as the "GM debate." Although the strength of the controversy varied considerably throughout the world, with much greater intensity in Europe than in the US, anxieties continued to focus on a number of potentially adverse environmental effects arising from GM foods. First, there are concerns that GM crops will indirectly reduce wild plant biodiversity through intensification of industrial agriculture (increased use of pesticides and herbicides) and potentially threaten species higher up the food chain, for example invertebrates that feed on the weeds, and their bird and mammal predators. Second, the debate has focused on the risk of cross-pollination and gene transfer between GM and non-GM plants. Contamination has implications for the labeling of foods, for organic methods, and for seed production. Finally, more intensive production methods, together with enhanced transportation tolerance, are seen to exacerbate other environmental problems, particularly pollution and global warming.

See also: Biotechnology, Breeding, Animal Genetic Methods; Breeding, Plant Genetic Methods; Gene Therapy; Genetic Engineering, Methods; Genetic Screening and Testing; Pesticides

Nik Brown

Further Reading

Advisory Committee on Novel Foods and Processes, Annual Report (2000), FSA/0013/0301
Boylan, Michael and Kevin E. Brown. Genetic Engineering: Science and Ethics on the New Frontier. Upper Saddle River, NJ: Prentice Hall, 2001

Bud, R. (1998) Molecular Biology and the Long-Term History of Biotechnology, in Cameron, N. D. Selection Indices and Prediction of Genetic Merit in Animal Breeding, Oxford: CAB International, 1997.

Reeve, E. (ed) Encyclopedia of Genetics, London and Chicago: Fitzroy Dearborn, 2000 (various articles, including Rice genetics: engineering vitamin A; Pharmaceutical proteins from milk of transgenic animals)

Thackray, A. (ed) Private Science: Biotechnology and the Rise of the Molecular Sciences. Philadelphia: University of Pennsylvania Press

Sample Entries