Genetic EngineeringGenetic engineering is the artificial alteration of the genetic composition (the "genome") of cells or organisms. Since the genome is transmitted to descendants, the alteration is self-perpetuating. Because the genome controls biological activities, its manipulation may significantly alter biological function. The broadest definition of genetic engineering includes the artificial selection of PLANTS and ANIMALS, practised consciously or inadvertently in the development of domesticated varieties since prehistory. Conscious artificial selection of humans (EUGENICS) has generally found disfavour, for a variety of sociological, ethical and biological reasons.The term genetic engineering was introduced when the artificial means to move genes (hereditary factors, segments of DNA) between remotely related species developed in the mid-1970s.
Interspecies Gene Transfer
Interspecies gene transfer occurs naturally; interspecies hybrids produced by sexual means can lead to new species with genetic components of both pre-existing species. Interspecies hybridization played an important role in the development of domesticated plants. Interspecies hybrids can also be produced artificiallly between sexually incompatible species. Cells of both plants and animals can be caused to fuse, producing viable hybrid cell-lines. Cultured hybrid plant cells can regenerate whole plants, so cell fusion allows crosses of sexually incompatible species. Most animal cells cannot regenerate whole individuals; however, the fusion of antibody-forming cells (which are difficult to culture) and "transformed" (cancer-like) cells, gives rise to immortal cell-lines, each producing one particular antibody, so-called monoclonal antibodies. These cell-lines can be used for the commercial production of diagnostic and antidisease antibody preparations. (Fusions involving human cells play a major role in investigations of human heredity and GENETIC DISEASE.)
In nature, the transfer of genes between sexually incompatible species also occurs; for example, genes can be carried between species during viral infection. In its most limited sense, genetic engineering exploits the possibility of such transfers between remotely related species. There are two principle methods. First, genes from one organism can be implanted within another, so that the implanted genes function in the host organism. Alternatively, the new host organism (often a micro-organism) produces quantities of the DNA segment that contains a foreign gene, which can then be analysed and modified in the test tube, before return to the species from which the gene originated. Dr Michael SMITH of the University of British Columbia was the corecipient of the 1993 NOBEL PRIZE in Chemistry for his invention of one of the most direct means to modify gene structure in the test tube, a technique known as in vitro mutagenesis.
The continuing development of modern genetic engineering depends upon a number of major technical advances: cloning, gene cloning and DNA sequencing.
Cloning is the production of a group of genetically identical cells or individuals from a single starting cell; all members of a clone are effectively genetically identical. Most single-celled organisms, many plants and a few multicellular animals form clones as a means of reproduction - "asexual" reproduction. In humans, identical twins are clones, developing after the separation of the earliest cells formed from a single fertilized egg.
Cloning is not strictly genetic engineering, since the genome normally remains unaltered, but it is a practical means to propagate engineered organisms.
In combination with test-tube fertilization and embryo transplants, Alta Genetics of Calgary is a world leader in the use of artificial twinning as a tool in the genetic engineering of cattle. Manipulating plant hormones in plant cell cultures can yield clones consisting of millions of plantlets, which may be packageable to form artificial seed.
Cloning of genetically engineered animals is generally difficult. Clones of frogs have been produced by transplanting identical nuclei from a single embryo, each to a different nucleus-free egg. This technique is not applicable to mammals. However, clones of cells derived from very young mammalian embryos (embryonic stem cells) can be used to reconstitute whole animals and are widely used for genetic engineering of mice. There is no reported instance of cloning of humans by any artificial means. Nonetheless, frequent calls for regulation of human cloning and genetic engineering occur, which stem from the same considerations that lead most commentators to reject eugenics.
Gene cloning is fundamental to genetic engineering. A segment of DNA from any donor organism is joined in the test tube to a second DNA molecule, known as a vector, to form a "recombinant " DNA molecule.
The design of appropriate vectors is an important practical area. Entry of DNA into each kind of cell is best mediated by different vectors. For BACTERIA, vectors are based on DNA molecules that move between cells in nature - bacterial VIRUSES and plasmids. Mammalian vectors usually derive from mammalian viruses. In higher plants, the favoured system is the infectious agent of crown-gall tumours.
Gene cloning in microbes has reached commercial application, notably with the marketing of human INSULIN produced by bacteria. Many similar products are now available, including growth hormones, blood-clotting factors and antiviral interferons. Gene cloning has revolutionized the understanding of genes, cells and diseases particularly of CANCER. It has raised the diagnosis of hereditary disease to high science, has contributed precise diagnostic tools for infectious disease and is fundamental to the use of DNA testing in forensic science.
The ability to clone genes led directly to the discovery of the means to analyse the precise chemical structure of DNA; that is, DNA sequencing. A worldwide co-operative project, the Human Genome Project, is now underway, with the object of cloning and sequencing the totality of human DNA, which contains perhaps 100 000 or more genes. To date, at least 80% of the DNA has been cloned and localized roughly within the human chromosome set. It is predicted that the sequencing will be effectively completed in less than 20 years. However, it is clear that the biological meaning of the DNA structure will take decades, if not centuries, to decipher.
To avoid potential hazards deriving from genetic engineering, gene cloning even in bacteria is publicly regulated in Canada and the US by the scientific granting agencies and in some other countries by law. Biological containment, the deliberate hereditary debilitation of host cells and vectors, is required. In using mammals and higher plants, especially strict regulations apply, requiring physical isolation.
A great deal of work remains, both in the development of techniques and in the acquisition of fundamental knowledge needed to apply the techniques appropriately. Nonetheless, genetic engineering promises a world of tailor-made CROP plants and farm animals; cures for hereditary disease by gene replacement therapy; an analytical understanding of cancer and its treatment; and a world in which much of our present-day harsh chemical technology is replaced by milder, organism-dependent, fermentation processing.
In Canada, genetic engineering research is taking place in the laboratories of universities, industries, and federal and provincial research organizations. In the industrial sector, medical applications are being developed, for example at Ayerst Laboratories, Montréal, AVENTIS PASTEUR LTD., Toronto, and theINSTITUT ARMAND-FRAPPIER, Laval-des-Rapides, Québec.
Inco is researching applications for MINING and METALLURGY, and LABATT'S BREWERIESis applying recombinant DNA techniques to brewing technologies. A large number of Canadian companies engage in the research and development of genetically engineered products, particularly in the area of PHARMACEUTICALS and medical diagnostics. As many as half of the federally operated NATIONAL RESEARCH COUNCIL Research Institutes have significant involvement with genetic engineering, including the Biotechnology Research Institute (Montréal) and the Plant Biotechnology Institute (Saskatoon), whose mandates are largely in this area. The Veterinary Infectious Disease Organization, based at University of Saskatchewan, is using genetic engineering technology for production of new vaccines for livestock diseases.
See also ANIMAL BREEDING; PLANT BREEDING; HUMAN GENOME PROJECT; BIOTECHNOLOGY; TRANSPLANTATION.