Science and technology of farm animal cloning: state of the art

Details of the first mammal born after nuclear transfer cloning were published by Steen Malte Willadsen in 1986. In spite of its enormous scientific significance, this discovery failed to trigger much public concern, possibly because the donor cells were derived from pre-implantation stage embryos. The major breakthrough in terms of public recognition has happened when Ian Wilmut et al. [Wilmut, I., Schnieke, A.E., McWhir, J., Kind, A.J., Campbell, K.H., 1997. Viable offspring derived from fetal és adult mammalian cells. Nature 385, 810-813] described the successful application of almost exactly the same method, but using the nuclei of somatic cells from an adult mammal, to create Dolly the sheep. It has become theoretically possible to produce an unlimited number of genetic replicates from an adult animal or a post-implantation foetus. Since 1997 a number of different species including pigs, goats, horses, cats, etc. have been cloned with the somatic cell nuclear transfer technique. Although the technology still has relatively low success rates and there seems to be substantial problems with the welfare of some of the cloned animals, cloning is used both within basic research and the biomedical sector. The next step seems to be to implement cloning in the agricultural production system and several animals have been developed in this direction. This article reviews the current state of the art of farm animal cloning from a scientific and technological perspective, describes the animal welfare problems and critically assess different applications of farm animal cloning. The scope is confined to animal biotechnologies in which the use of cell nuclear transfer is an essential part and extends to both biomedical and agricultural applications of farm animal cloning. These applications include the production of genetically identical animals for research purposes, and also the creation of genetically modified animals. In the agricultural sector, cloning can be used as a tool within farm animal breeding. We do not intend to give an exhaustive review of the all the literature available; instead we pinpoint issues and events pivotal to the development of current farm animal cloning practices and their possible applications.     

Thirty years after Brambell: whither animal welfare science?

It has been just over 30 years since the Brambell Committee issued its clarion call for research on the welfare of animals used in agriculture. What progress has farm animal welfare science made in those 30 years, and what challenges will it face in the next 30? In this article, I discuss the ways in which the Brambell report, with its emphasis on behavioral needs and suffering, both propelled and constrained the development of animal welfare science. The role that economic factors play and the ways in which they have imposed other kinds of constraints on scientists working with farm animals are also mentioned. Despite these constraints, animal welfare science has contributed to a number of significant improvements in the welfare of farm animals. There is, however, a growing sense that animal welfare science has reached an impasse and that ethical and scientific questions about animal welfare have become hopelessly entangled. In this context, I address what I view to be the principal challenge facing farm animal welfare science, namely to move the issue of beyond suffering to an evaluation of broader quality-of-life questions and their application to improvements in welfare.     

Ethical, legal, and social aspects of farm animal cloning in the 6th Framework Programme for Research

Cloned livestock have potential importance in the provision of improved medicine as well as in the development of livestock production. The public is, however, increasingly concerned about the social and ethical consequences of these advances in knowledge and techniques. There is unevenness throughout Europe in different Member States' attitudes to research into livestock cloning. Although there is EU legislation controlling the use of animals for research purposes, there is no legislation specifically governing cloning in livestock production. The main EU reference is the 9th Opinion of the European Group on Ethics, which states "Cloning of farm animals may prove to be of medical and agricultural as well as economic benefit. It is acceptable only when the aims and methods are ethically justified and when carried out under ethical conditions." The ethical justification includes the avoidance of suffering, the use of the 3Rs principle and a lack of better alternatives. The Commission addresses these issues in the 6th Framework Programme by promoting the integration of ethical, legal and social aspects in all proposals where they are relevant, by fostering ethical awareness and foresight in the proposals, by encouraging public dialogue, and by supporting specific actions to promote the debate. Research must respect fundamental ethical principles, including animal welfare requirements.     

New commercial opportunities for advanced reproductive technologies in horses,wildlife, and companion animals

As advanced reproductive technologies become more efficient and repeatable in livestock and laboratory species, new opportunities will evolve to apply these techniques to alternative and non-traditional species. This will result in new markets requiring unique business models that address issues of animal welfare and consumer acceptance on a much different level than the livestock sector. Advanced reproductive technologies and genetic engineering will be applied to each species in innovative ways to provide breeders more alternatives for the preservation and propagation of elite animals in each sector. The commercialization of advanced reproductive techniques in these niche markets should be considered a useful tool for conservation of genetic material from endangered or unique animals as well as production of biomedical models of human disease.     

Agricultural (nonbiomedical) animal research outside the laboratory: a review of guidelines for institutional animal care and use committees

Challenges and published guidelines associated with appropriate care and use of farm animals in agricultural research conducted outside the laboratory are briefly reviewed. The Animal Welfare Act (Title 9 of the 2000 Code of Federal Regulations), which regulates the care and use of agricultural animals in biomedical research, does not include livestock and poultry used in agricultural research. Farm animal research funded (and thereby regulated) by the US Public Health Service is further discussed in the National Research Council's 1996 Guide for the Care and Use of Laboratory Animals. However, neither of these guidelines adequately addresses the unique attributes of research and teaching designed to improve production agriculture. That information is contained in the Guide for the Care and Use of Agricultural Animals in Agricultural Research and Teaching (the Ag Guide), published by the Federation of Animal Science Societies in 1999. The Ag Guide provides excellent general recommendations for agricultural animal research. It serves as an invaluable resource for institutional animal care and use committees, which attempt to balance the welfare of farm animals and the needs of those working to improve animal agriculture.     

Genetically modified laboratory animals--what welfare problems do they face?

In this article, we respond to public concern expressed about the welfare of genetically modified (GM) nonhuman animals. As a contribution to the debate on this subject, we attempt in this article to determine in what situations the practice of genetic modification in rodents may generate significant welfare problems. After a brief discussion of the principles of animal welfare, we focus on the problem of animal suffering and review some types of gene modifications likely to cause predictable welfare problems. In this article, we also consider suffering that may be involved in the process of generating GM animals. Finally, we discuss the role of GM animals in attempts to reduce, replace, and refine the use of animals in research.     

A guide to defining and implementing protocols for the welfare assessment of laboratory animals: eleventh report of the BVAAWF/FRAME/RSPCA/UFAW Joint Working Group on Refinement

The refinement of husbandry and procedures to reduce animal suffering and improve welfare is an essential component of humane science. Successful refinement depends upon the ability to assess animal welfare effectively, and detect any signs of pain or distress as rapidly as possible, so that any suffering can be alleviated. This document provides practical guidance on setting up and operating effective protocols for the welfare assessment of animals used in research and testing. It sets out general principles for more objective observation of animals, recognizing and assessing indicators of pain or distress and tailoring these to individual projects. Systems for recording indicators, including score sheets, are reviewed and guidance is set out on determining practical monitoring regimes that are more likely to detect any signs of suffering. This guidance is intended for all staff required to assess or monitor animal welfare, including animal technologists and care staff, veterinarians and scientists. It will also be of use to members of ethics or animal care and use committees. A longer version of this document, with further background information and extra topics including training and information sharing, is available on the Laboratory Animals website.     

In Memoriam

Practicing physicians are just becoming aware of the animal rights movement, which during the 1980s spawned numerous acts of violence against research facilities throughout the United States. The animal rightists are challenging physicians to show moral justification for the human exploitation of nature and the world of subhuman species. They have aroused public interest in animal welfare, sparked protective legislation for experimental animals, and indirectly encouraged the creation of committees to oversee the conduct of animal experimentation and the conditions of animal confinement. This controversy has necessitated a closer look at the questions of animal experimentation and animal rights against the backdrop of human experimentation and human rights. Physicians and specialists in animal care seek to alleviate suffering and anxiety, and, as moderates, they may be able to bring both sides of the animal rights controversy together in a spirit of mutual tolerance and in the common cause of promoting both human and animal welfare.     

Ethical review in biomedical research

Through the difficulties encountered during the previous centuries in order for an animal to be recognized as a sensitive being, we saw the evolution of society's attitudes change from antiquity to our present day. Over the past twenty years animal testing has first evolved within a progressive regulatory framework reinforced by an ethical thinking which has, since 1990, led to the establishment of the ethics committees. The dialogue between these committees and researchers has led to the recovery of principles previously ignored such as the 3Rs (Replace, Reduce, Refine). This in turn has led to the application of improving experimental conditions, the progressive decrease in the number of animals used through a wise use and the replacement of animals by in vitro techniques in the very preliminary stages of research. Progress remains to be done, but the evolution of European regulations being amended, the formalization in France of ethics committees and the establishment of the National Ethics Committee should further contribute to the improvement of animal welfare in experimental research.     

A Survey of Chinese Citizens’ Perceptions on Farm Animal Welfare

Farm animal welfare has been gradually recognized as an important issue in most parts of the world. In China, domestic animals were traditionally raised in backyard and treated as an important component of family wealth. Industrialization of animal production brings forth the farm animal welfare concerns recently in China, yet the modern concept of animal welfare has not been publicized and a comprehensive recognition on how consumers and farmers perceive animal welfare is lacking. Therefore, we conducted a survey on public opinions toward farm animal welfare in China, based on pigs (including sows, piglets, and fattening pigs), domestic fowls (including layers and broilers) and their products. From 6,006 effective questionnaires approximately two thirds of the respondents had never heard of ‘animal welfare’; 72.9% of the respondents claimed that, for the sake of animal derived food safety, human beings should improve the rearing conditions for pigs and domestic fowls; 65.8% of the respondents totally or partly agreed on establishing laws to improve animal welfare; more than half of the respondents were willing, or to some extent willing, to pay more for high-welfare animal products, whereas 45.5% of the respondents were not willing or reluctant to pay more. In summary, farm animal welfare is still in its early stage of development and more efforts are needed to improve the public conception to animal welfare in the process of establishing farm animal welfare standards and legislations in China.     

Genomics for food safety and sustainable animal production

There is a growing concern in society about the safety of animal-derived food, the health and welfare of farm animals and the sustainability of current animal production systems. Along farm animal, breeding genomics may contribute to a solution for these concerns. The use of genomic analysis tools, to achieve genetic progress in typical out-bred populations of farm animals, seems to be more difficult compared to 'model' organisms or plants. However, identification of positional candidate genes may be accelerated by linkage disequilibrium (LD) mapping. Recording of sustainable traits requires a large financial and logistic input and the economic advantages for the market are not as clear as for traditional selection traits. Examples show that the major genes causing variability for similar traits in different species are rarely the same. Therefore, for breeding purposes genomic analysis of the species of interest is needed. The fundamental knowledge obtained on the genetic architecture of complex traits will open new perspectives for the use of DNA tests in selection schemes. For food safety and traceability, DNA-based techniques evolve for monitoring and early warning systems.     

Genetic modification of animals in the next century

Since the initial demonstration in 1982 of profound phenotypic effects stemming from the expression of a single transgene, genetic engineering has revolutionized fundamental biological and biomedical research. The application of transgenic technology to farm animals has held the promise of being able to improve animal agriculture significantly and has resulted in a new industry, i.e., the successful expression of foreign proteins in the mammary gland for the pharmaceutical industry. Work over the last few years in model species (e.g., the mouse) and new technical developments such as cloning have now set the stage for the initial application of transgenic technology for the improvement of farm animals. Major limitations that remain are the lack understanding of which genes we should transfer in order to alter quantitative production traits usefully and the low efficiency of producting transgenic founders. Furthermore, more research is needed concerning the consequences and potential problems arising from the integration of transgenes into populations with varying genetic backgrounds. Recent advances suggest that within the first decade of the 21 st century the first transgenic animals will become available to the livestock industry, with acceptance depending upon their cost versus their potential economic benefit to the producers.     

Willingness to Pay: Australian Consumers and “On the Farm” Welfare

The success of welfare legislation for nonhuman animals rests upon primary producer compliance that, in turn, is affected by public willingness to pay (WTP) for such initiatives. Although the topic of the welfare of animals on farms (and relevant legislation) is becoming increasingly important to the Australian public, there remain relatively few recent assessments of the variables that may affect WTP and, therefore, support initiatives aimed at improving the welfare of animals living on farms. This study surveyed 1,224 community members in Queensland, Australia. The study assessed respondents' self-rated knowledge of, and concern regarding, farm animal welfare. In addition, the survey asked respondents how much more they would be prepared to pay for animal-based products to ensure that they came from a source where the Five Freedoms were met. Although self-rated knowledge and level of concern were found to affect WTP, the study found only concern for farm animal welfare actually predicted consumer behavior. Further analyses showed a potential confound between knowledge levels and locality. This article discusses the implications of this for future initiatives to increase WTP.     

Trapping and marking terrestrial mammals for research: integrating ethics, performance criteria, techniques, and common sense

We propose that researchers integrate ethics, performance criteria, techniques, and common sense when developing research trapping programs and in which members of institutional animal care and use committees address these topics when evaluating research protocols. To ask questions about ethics is in the best tradition of science, and researchers must be familiar with codes of ethics and guidelines for research published by professional societies. Researchers should always work to improve research methods and to decrease the effects on research animals, if for no other reason than to minimize the chances that the methods influence the animals' behavior in ways that affect research results. Traps used in research should meet performance criteria that address state-of-the-art trapping technology and that optimize animal welfare conditions within the context of the research. The proposal includes the following criteria for traps used in research: As Criterion I, killing-traps should render >/= 70% of animals caught irreversibly unconscious in /= 70% of animals with 相似文献   

Expanding the three Rs to meet new challenges in humane animal experimentation

The Three Rs are the main principles used by Animal Ethics Committees in the governance of animal experimentation, but they appear not to cover some ethical issues that arise today. These include: a) claims that certain species should be exempted on principle from harmful research; b) increased emphasis on enhancing quality of life of research animals; c) research involving genetically modified (GM) animals; and d) animals bred as models of disease. In some cases, the Three Rs can be extended to cover these developments. The burgeoning use of GM animals in science calls for new forms of reduction through improved genetic modification technology, plus continued attention to alternative approaches and cost-benefit analyses that include the large numbers of animals involved indirectly. The adoption of more expanded definitions of refinement that go beyond minimising distress will capture concerns for enhancing the quality of life of animals through improved husbandry and handling. Targeting refinement to the unpredictable effects of gene modification may be difficult; in these cases, careful attention to monitoring and endpoints are the obvious options. Refinement can also include sharing data about the welfare impacts of gene modifications, and modelling earlier stages of disease, in order to reduce the potential suffering caused to disease models. Other issues may require a move beyond the Three Rs. Certain levels of harm, or numbers and use of certain species, may be unacceptable, regardless of potential benefits. This can be addressed by supplementing the utilitarian basis of the Three Rs with principles based on deontological and relational ethics. The Three Rs remain very useful, but they require thoughtful interpretation and expansion in order for Animal Ethics Committees to address the full range of issues in animal-based research.     

Genetic Engineering and Other Factors That Might Affect Human-Animal Interactions in the Research Setting

Evidence exists, particularly in the welfare literature of nonhuman animals on the farm, that the interaction between nonhuman animals and the personnel who care for them can have a strong effect on the animals' behavior, productivity, and welfare. Among species commonly used for biomedical research, mice appear to be the least-preferred species in animal care facilities. A review of the literature and observations of animal care staff interacting with mice indicated that the following factors may influence this: their small size, their particular behavioral characteristics, and husbandry constraints (such as housing in ventilated racks). In addition, this study questioned whether animal care personnel have a different perception of genetically engineered animals and whether this, in turn, has an effect on their interactions with these animals. The ability to carefully observe an animal's behavior is key in carrying out an animal-wellness assessment and in minimizing pain and distress. Attention to human-animal interactions in the research setting represents an opportunity for refinement for large numbers of animals and potentially for reduction of animal use.     

Ethical issues concerning animal research outside the laboratory

Unique ethical issues can be associated with research outside the customary laboratory setting. Protocols involving wild animals must consider that any infringement on the wild nature of the species can be disruptive and may involve pain, fear, anxiety, and frustration, all of which constitute ethical harm that must be balanced with anticipated benefit. Agricultural and companion animal research, however, take place in a human-engineered environment and involves domesticated species adapted to human contact. Special animal welfare issues can be related to agricultural production goals that fail to deal adequately with moral concerns. Human/companion animal relationships, on the other hand, present unique moral obligations to animal owners. Other factors may present additional ethical issues when research is performed outside the laboratory. These factors include a required sensitivity to the environment of wild animals and an awareness that this outside research may to quite public and, therefore, vulnerable to community perception. The institutional animal care and use committee(IACUC) has the responsibility to ensure that research in outside settings is ethical and properly implemented. This responsibility requires that IACUC members have knowledge of the needs of a wide range of species and that a process is in place to allow effective monitoring of research in remote locations. Finally, and most important, there must be a sensitivity to the unique ethical considerations outlined here. Armed with these strengths, the IACUC will be effective in what may be unfamiliar surroundings and will have a significant opportunity to cause improvements in animal welfare.     

Contribution of pathology to laboratory animal welfare

To promote experimental animal welfare, several countries are engaged in establishing local animal research review committees and appointing supervising veterinarians or other experts. However, a number of adverse conditions leading to intercurrent illness or death remains unnoticed or unidentified. Pathological investigation of unexpectedly ill or dead animals proved to be very useful in indicating conditions compromising animal welfare. In addition, such post-mortem findings may be instructive, with respect to welfare, for those involved in experiments with animals.     

Reflecting on ethical and legal issues in wildlife disease

Disease in wildlife raises a number of issues that have not been widely considered in the bioethical literature. However, wildlife disease has major implications for human welfare. The majority of emerging human infectious diseases are zoonotic: that is, they occur in humans by cross‐species transmission from animal hosts. Managing these diseases often involves balancing concerns with human health against animal welfare and conservation concerns. Many infectious diseases of domestic animals are shared with wild animals, although it is often unclear whether the infection spills over from wild animals to domestic animals or vice versa. Culling is the standard means of managing such diseases, bringing economic considerations, animal welfare and conservation into conflict. Infectious diseases are also major threatening processes in conservation biology and their appropriate management by culling, vaccination or treatment raises substantial animal ethics issues. One particular issue of great significance in Australia is an ongoing research program to develop genetically modified pathogens to control vertebrate pests including rabbits, foxes and house mice. Release of any self‐replicating GMO vertebrate pathogen gives rise to a whole series of ethical questions. We briefly review current Australian legal responses to these problems. Finally, we present two unresolved problems of general importance that are exemplified by wildlife disease. First, to what extent can or should ‘bioethics’ be broadened beyond direct concerns with human welfare to animal welfare and environmental welfare? Second, how should the irreducible uncertainty of ecological systems be accounted for in ethical decision making?     

Use of biophotonic imaging as a training aid for administration of substances in laboratory rodents

Dosing of experimental animals and the removal of blood are two of the most frequent procedures performed in biomedical research using live animals. Despite the apparently simple nature of these procedures, they can, if not correctly carried out, have significant effects on the welfare of the animals and the scientific value of the results. There are several methods by which research staff may obtain training in the administration of substances. These include practical demonstrations during teaching courses; observation of techniques; videos and educational computer programs and practising on recently killed animal cadavers or plastic animal models. Each method has its own advantages and disadvantages. A common factor encountered during training is the difficulty in assessing competency. This paper reports a pilot study on the use of bioluminescent imaging technology to assess competency in the administration of substances to rodents. Bioluminescence was rapidly detected after dosing of animals with a bioluminescent substance. However, living animals were required for a signal to be generated. The data presented suggest that this technology is ideal for use as a teaching aid and may also prove valuable in assessing the effectiveness of 'complex' and novel administration routes in 'realtime'.