[Report by the Committee on the Studies of Standard for Genetic Engineering].
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Reproductive and genetic engineering are presented by their promoters as miracle cures for people with infertility problems or who are at genetic risk in having their desired healthy child. Focusing on the test-tube baby method (in vitro fertilization), in this article I investigate the medical reality of these technologies and their impact on women's lives as individuals and as members of a social group, women. Specifically, I discuss these developments in a global context and suggest that, in connection with fertility-control methods, they could be used as the ultimate means of population control. I contend that reproductive and genetic engineering dismember, fragment, and dissect women into their body parts and that, in the interests of women with a right to bodily integrity and dignity, they need to be stopped.
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Modern genetic engineering technologies enable us to manipulate the mouse genome in increasingly complex ways to model human biology and disease. As a result, the number of mouse strains carrying transgenes or induced mutations has increased markedly. Thorough understanding of strain and gene nomenclature is essential to ensure that investigators know what kind of mouse they have, and what to expect in terms of phenotype. Genetically engineered mice alter gene function by over-expressing, eliminating, or modifying a gene product. The resulting phenotype is often unexpected and not completely understood, necessitating special care and potentially complex breeding and husbandry strategies. Animal care technicians responsible for routine maintenance of the colony, facility managers, veterinarians, and research personnel working with mice should be well informed about the nature of the mutation, distinguishing characteristics, and necessary precautions in handling the mice. Personnel working with mice also must be aware of the multitude of factors intrinsic to the mouse and present in the environment that can influence reproductive performance. Finally, diligent adherence to the maintenance of genetic quality in conjunction with cryopreservation of germplasm is the best insurance against loss of a colony.
Genetically engineered Mengo viruses with artificial deletions in the 5' noncoding poly(C) tracts are highly attenuated for pathogenicity when introduced as live vaccines into the natural murine host. Inoculation produces lifelong protective immunity without disease or viral persistence. This report extends the vaccination studies to non-murine hosts, including baboons, macaques and domestic pigs, all of which are susceptible to severe cardiovirus epizootics. All animals of these species that were inoculated with vMC24, an engineered strain of Mengo, seroconverted. When the immunized animals were challenged, they were protected against lethal doses of encephalomyocarditis virus (EMCV) derived from currently circulating epizootic strains. In baboons, the neutralizing antibody titers induced by vMC24 were significantly higher than from an inactivated EMCV vaccine. Moreover, terminal histopathology on baboons (inoculated intramuscularly), macaques (inoculated intracerebrally), and pigs (inoculated intramuscularly) showed few, if any, gross lesions characteristic of EMCV-like disease, in the vMC24 vaccinates. We suggest that genetically engineered, short poly(C) Mengo viruses may be universally potent attenuated vaccines for many types of animals and can possibly provide safe, efficacious protection against all cardioviruses of the EMCV serotype.
The benefits of genetic engineering of crop plants to improve the reliability and quality of the world food supply have been contrasted with public concerns raised about the food safety of the resulting products. Debates have concentrated on the possible unforeseen risks associated with the accumulation of new metabolites in crop plants that may contribute to toxins, allergens and genetic hazards in the human diet. This review examines the various molecular and biochemical mechanisms by which new hazards may appear in foods as a direct consequence of genetic engineering in crop plants. Such hazards may arise from the expression products of the inserted genes, secondary or pleiotropic effects of transgene expression, and random insertional mutagenic effects resulting from transgene integration into plant genomes. However, when traditional plant breeding is evaluated in the same context, these mechanisms are no different from those that have been widely accepted from the past use of new cultivars in agriculture. The risks associated with the introduction of new genes via genetic engineering must be considered alongside the common breeding practice of introgressing large fragments of chromatin from related wild species into crop cultivars. The large proportion of such introgressed DNA involves genes of unknown function linked to the trait of interest such as pest or disease resistance. In this context, the potential risks of introducing new food hazards from the applications of genetic engineering are no different from the risks that might be anticipated from genetic manipulation of crops via traditional breeding. In many respects, the precise manner in which genetic engineering can control the nature and expression of the transferred DNA offers greater confidence for producing the desired outcome compared with traditional breeding.
Commercial genetic engineering is advancing into areas that require the small-scale introduction of genetically engineered microorganisms (GEMs) to better quantify variables that affect microorganism distribution and survival and to document potential long-term consequences. A recombinant DNA marker system, the lacZY marker, developed by the Monsanto Agricultural Co., enables the distribution and fate of marked fluorescent pseudomonad organisms to be monitored under actual field conditions. Critical evaluation of GEMs under field conditions is imperative if plant-beneficial effects are to be correlated with organism release. This paper evaluates the effectiveness of this marker system and its ability to facilitate the assessment of risks associated with deliberate environmental introductions of genetically engineered microorganisms. Results of prerelease contained growth chamber and field experiments demonstrated that: (1) the scientific risk assessment methodology adopted by Monsanto and approved by the U.S. Environmental Protection Agency was appropriate and comprehensive; (2) the deliberate introduction of a GEM did not pose unacceptable or unforeseen risks to human health or the environment; (3) the lacZY marker is an effective environmental tracking tool; and (4) regulatory oversight should reflect the expected risk and not be excessively burdensome for all GEMs.
Microencapsulated genetically engineered cells have the potential to treat a wide range of diseases. For example, in experimental animals, implanted microencapsulated cells have been used to secrete growth hormone to treat dwarfism, neurotrophic factors for amyotrophic lateral sclerosis, beta-endorphin to decrease pain, factor XI for hemophilia B, and nerve growth factors to protect axotomized neurons. For some applications, microencapsulated cells can even be given orally. They can be engineered to remove unwanted molecules from the body as they travel through the intestine, and are finally excreted in the stool without being retained in the body. This application has enormous potential for the removal of urea in kidney failure, ammonia in liver failure and amino acids such as phenylalanine in phenylketonuria and other inborn errors of metabolism.
Genetic engineering of non-beta cells to release insulin upon feeding could be a therapeutic modality for patients with diabetes. A tumor-derived K-cell line was induced to produce human insulin by providing the cells with the human insulin gene linked to the 5'-regulatory region of the gene encoding glucose-dependent insulinotropic polypeptide (GIP). Mice expressing this transgene produced human insulin specifically in gut K cells. This insulin protected the mice from developing diabetes and maintained glucose tolerance after destruction of the native insulin-producing beta cells.
The commercialization of genetically engineered food animals will pose a number of legal and regulatory questions. These may be grouped into questions of process and questions of products. The process of animal genetic engineering with artificially constructed vectors will probably be regulated in much the same manner as other veterinary procedures. There may be some discussion, however, as to whether animal drug or animal biologic regulations are more applicable. The products of animal genetic engineering, i.e., transgenic food animals and food products made from them, also raise important questions about product safety and identity. These include whether and how genetically engineered food animals will be subject to federal inspection for wholesomeness, whether artificial vectors, foreign genes, or gene products will adulterate recipient animal tissues, and how food products made from such animals will be labeled. Prior federal experience with the inspection of interspecific hybrids of cattle and buffalo provides a useful basis for further policy developments in the inspection and labeling of genetically engineered food animals. In particular, the inspection of cattle/buffalo hybrids has established a phenotypic (based on appearance) criterion for deciding how novel food animals should be inspected. As the genetic engineering of food animals on a production basis draws nearer, it may be necessary to supplement the phenotypic criterion with genetic (based on pedigree) criteria to assure that the essential characteristics of animals slaughtered under current food statutes are maintained.
Genetic engineers have been remiss in addressing ethical and social issues emerging from this powerful new technology, a technology whose, implications for agriculture are profound. As a consequence of this failure, society has been uneasy about genetic engineering of animals and has had difficulty distinguishing between genuine and spurious ethical issues the technology occasions. Many of the most prominent concerns do not require a serious response. On the other hand, concerns about a variety of possible risks arising from genetic engineering of animals require careful consideration and dialogue with the public. Such concerns are an admixture of ethics and prudence. A purely ethical challenge, however, hitherto not addressed, is represented by problems of animal welfare that arise out of genetically engineering agricultural animals. A principle of "conservation of welfare" is suggested as a plausible moral rule to guide such genetic engineering.
Plans to introduce genetically engineered microorganisms into the environment has led to concerns over safety and has raised questions about how to detect and to contain such microorganisms. Specific gene sequences, such as lacZ, have been inserted into genetically engineered microorganisms to permit their phenotypic detection. Molecular methods have been developed based upon recovery of DNA from environmental samples and gene probe hybridization to specific diagnostic gene sequences for the specific detection of genetically engineered microorganisms. DNA amplification using the polymerase chain reaction has been applied to enhance detection sensitivity so that single gene targets can be detected. Detection of messenger RNA has permitted the monitoring of gene expression in the environment. The use of reporter genes, such as the lux gene for bioluminescence, likewise has permitted the observation of gene expression. Conditional lethal constructs have been developed as models for containment of genetically engineered microorganisms. Suicide vectors, based upon the hok gene have been developed as model containment systems.
Technical developments of genetic engineering have been revealed especially interesting in the human therapeutic field. Techniques for gene transfer have been improved to introduce synthetic sequences into the cellular genomes. Candidate cells and culture systems have been screened for their capacity to synthesise the proper recombinant molecules. In the nearest future, high biotechnologies should provide a great quantity of recombinant products, covering a high variety of diseases (clotting factors, cytokines, hormones, monoclonal antibodies, vaccines, thrombolytics). This tendency has been largely initiated, and is accompanied by the quick development of basic sciences such as glycobiology and molecular biology, together with the development of a specific regulatory environment. Besides, genetic engineering offers new therapeutic outlets: transgenic animals, genic therapy, antisense technology.
Examples for genetic engineering are the transfer of nuclei between cells of higher animals and the introduction of heterologous DNA into bacteria by means of plasmids. The former approach will help to establish new ways in animal breeding, the latter provides bacterial cells that produce proteins of medical importance. The moral justification of related studies in man is still open, but the possible risks of gene technology can be coped with by adhering to proper safety regulations.
Genetic engineering of livestock is expected to have a major effect on the agricultural industry. However, accurate assessment of the consequences of transgene expression is impossible without multigenerational studies. A systematic study of the beneficial and adverse consequences of long-term elevations in the plasma levels of bovine growth hormone (bGH) was conducted on two lines of transgenic pigs. Two successive generations of pigs expressing the bGH gene showed significant improvements in both daily weight gain and feed efficiency and exhibited changes in carcass composition that included a marked reduction in subcutaneous fat. However, long-term elevation of bGH was generally detrimental to health: the pigs had a high incidence of gastric ulcers, arthritis, cardiomegaly, dermatitis, and renal disease. The ability to produce pigs exhibiting only the beneficial, growth-promoting effects of growth hormone by a transgenic approach may require better control of transgene expression, a different genetic background, or a modified husbandry regimen.
Genetically engineered microorganism ecology has been one of main research contents in microorganism molecular ecology. Along with the introduction of molecular marker and molecular biology, traditional microorganism ecology has been developed; therefore, it is possible to study the relationship between GEM and environment, environmental microorganism under molecular level. The GEM ecology has become a new and intersection borderline discipline, related to molecular biology, microbiology, ecology and so on. Moreover, it brought forward that the prosecution of the research on the transgenic organism ecology and the risk assessment, and the foundation of checking means and valuating standard that adapt to the situation of China could help to the development of GEM ecology in China.
Genetically engineered E. coli, which express both a Hg2+ transport system and metallothionein, were tested for their ability to remove mercury from wastewater. The wastewater contained more than ten different ions, including 2.58 mg/l mercury, and its pH was 9.6. Mercury uptake was faster from the wastewater than from distilled water, probably because of the higher ionic strength, as the high pH had little effect on mercury accumulation. EDTA also stimulated mercury uptake rather than inhibiting it. A hollow-fiber bioreactor was used to retain induced cells for continuous mercury uptake. The cells removed more than 99% of the mercury in the wastewater and the final amount of mercury accumulated was 26.8 mg/g cell dry weight, while none of the other ions were removed from the water. These results indicated that the induced cells had a high affinity and specificity for mercury.
It sometimes seems that genetic engineering is suspect, both to its practitioners and to the general public, because it is perceived as being somehow unnatural. This essay argues, on the basis of an analysis of two senses of "natural," that there is nothing distinctively morally problematic about genetic engineering, at least on the grounds of its alleged unnaturalness. It does not follow that we cannot distinguish among morally legitimate and morally suspect uses of genetic engineering. But these distinctions can and should be drawn on the basis of the same considerations that enter into the evaluation of particular uses of any other medical procedure.