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PLENARY AND SPECIAL LECTURESPLENARY SESSION I: POLICY The 3rd World Congress (1999, Bologna) celebrated the fortieth anniversary of the publication of Russell and Burch's The Principles of Humane Experimental Technique. There was the general notion that the Three R's offer a unifying concept that contributes to the quality of research and to a progressive reduction in animal use without compromising human health or the protection of the environment. The Bologna Three R's Declaration was accepted unanimously, calling upon all parties involved to incorporate the Three R's into animal-based research. Now four years later, the question may be raised whether the Declaration, indeed, served as a stimulus for the acceptance of the Three R's and, in particular, for the development and implementation of validated alternative methods. Information on animal use and alternatives has been collected from European countries, Canada, and the United States. The results of this survey will be presented, thus providing an overview on the current status in these countries with respect to:
The conclusion reached is that, with more emphasis on education and implementation of alternative methods, the number of animals used in research and testing can be further decreased in the near decades. PLENARY SESSION II: REPLACEMENT AND REDUCTION Toxicology is the science of adverse effects of chemicals, drugs, environmental agents, and stressors. Genomics defines the structure, sequence (code), and function of the entire DNA complement of organisms. The interface of these diverse disciplines is called toxicogenomics and is based upon the application of genomic technologies to define globally the changes in gene expression (both mRNA and proteins) as a consequence of exposures. DNA microarray technology enables the simultaneous measurement of transcription of thousands of genes using microchips containing thousands of probes of complementary DNA (cDNA) immobilized in a predetermined array. The ultimate application of this technology to toxicology holds great promise but faces several formidable problems. With the solution to these problems, it will be possible to develop a substantial database of Chemical Effects in Biological Systems (CEBS). Such a database will provide the capacity to relate specific changes in gene expression to specific adverse effects and to look for similar pathways in different organisms. Such data will provide an objective way of assessing surrogate systems for reporting or predicting potential adverse effects in humans. While the potential for toxicogenomics is thus very high for identifying true informative surrogate models, the task must be approached in a deliberate, incremental manner to insure that only high quality data are compiled and analyzed. PLENARY SESSION III: ETHICS The New Zealand Royal Commission on Genetic Modification was directed to investigate the strategic options available to address the use of genetically modified organisms and products. The Commission spent 14 months hearing submissions in public meetings and formal hearings. Over 10,000 written public submissions were received. Most were against any use of the technology in food, and many were angry at lack of product labeling, and, therefore, choice. Few were supportive; however, there was little objection to use of genetic technology or modified organisms in containment, especially for medical research. Many New Zealanders had strong spiritual objections to creation of transgenic animals containing human DNA, which they described as "playing God" or "interfering with Nature." Many expressed a lack of trust in scientists and biotechnology companies. Despite these views, the Commission concluded that New Zealand should keep its options open and proceed carefully, minimizing and managing risks. We recommended that Government establish a Bioethics Council to act as a transparent advisory body and to prepare guidelines on biotechnology, enabling public education and participation in decision-making. PLENARY SESSION IV: EDUCATION During the last decade, a large number of sophisticated alternatives to the use of animals in education have been developed. Information about these alternatives is now readily available from a variety of sources. Many countries have adopted legislation forbidding the unnecessary use of live animals in teaching. Educators wishing to retain the use of animals or animal products meet increasing opposition from individual students and local animal welfare organizations. This opposition is even evident in professional studies, such as veterinary medicine, where students clearly need to acquire considerable practical skills before they can be considered competent to treat their future patients. In addition, large student classes and limited availability of animals needing veterinary treatment often add to the difficulties of designing teaching programs. This presentation examines the arguments for and against the continued use of animals in education, outlines the alternatives available, provides an overview of information sources, and reports on the results of efforts to introduce alternatives, with special emphasis on higher education. Finally, the author proposes a set of guidelines that educational establishments may use in designing ethically acceptable curricula within the biomedical sciences. PLENARY SESSION V: REPLACEMENT The biomedical sciences are crossing a watershed. Fifteen years ago, when the human genome project was first proposed, biomedical research was almost purely experimental. Today, advanced computation and mathematics is becoming increasingly common, and during the coming decades, we can expect biology to become the most computationally intensive of all the sciences. Along with this change is the introduction of very high throughput experimental technologies, including various micro-array and display technologies. I will give three examples of technologies that will have profound effects on the way information about living systems is acquired and analyzed: genomics and cell systems biology in the development of disease diagnostics; computer simulations of whole organs and their interrelation under various kinds of stress; and display technologies and their use in obtaining reagents that formerly required large numbers of animals. PLENARY SESSION VI: REFINEMENT The notion that strategies that promote animal welfare benefit scientific outcomes would seem to be self-evident. Methods that, either separately or in combination, minimize an animal's experience of pain or distress or promote its sense of well-being are key elements in promoting its welfare. Due to the diversity of situations that are presented in the research setting, a flexible approach is essential to achieve these goals; specific issues need to be identified and addressed on a case-by-case basis. Nevertheless, strategies that are used fall into three broad categories: 1) the management of pain an distress through pharmacological intervention, 2) the refinement of techniques or protocols to minimize the impact of a particular procedure or process, and 3) providing a living experience that promotes an animal's sense of comfort and well-being, which may enable it to better cope with stress and possibly modulate its experiences of pain or distress. This paper will discuss the implications for scientific outcomes of adopting these three approaches. PLENARY SESSION VII: VALIDATION Chemical allergy is an important occupational and environmental health issue, and there is a need to identify and characterize chemicals that have the potential to induce sensitization. In the context of the toxicological assessment of skin sensitizing, activity the design, development, evaluation, and validation of the local lymph node assay (LLNA) has allowed a more rational approach to hazard identification and determination of relative potency in the context of risk assessment. Moreover, the method provides important animal welfare benefits, in terms of both reduction and refinement. Lessons learned from the LLNA that are relevant to the future development of alternative test methods will be discussed. In addition, a detailed appreciation of the immuno-biological mechanisms responsible for the acquisition of sensitization to chemical allergens has created new opportunities to refine further strategies for toxicological evaluation. These advances, and the new approaches they have facilitated, will be considered.
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