of behavioral assessment of transgenic mice see Appendix). Moreover, the improvements in husbandry that support the successful creation of transgenic and genetically modified (GM) colonies, could provide clues for refinement of breeding and husbandry procedures in the non-GM laboratory animal world. This knowledge will enable further investigation into the conditions under which stress or distress do (or do not) alter the course of a disease.

  • Should IACUCs, preclinical study safety officers, and scientific journal editors establish criteria by which historically acceptable control animals would suffice for statistical comparisons in certain situations? If otherwise scientifically and methodologically valid (more information on the challenges of using historical controls in Chapter 4), such a change would reduce the number of control animals used in potentially or intentionally distress-inducing protocols. Standardization and awareness of key Three Rs-related words and concepts among editors and reviewers would promote their application, especially in refinements. In a similar spirit, could the often useful but underappreciated approach of humans serving as the “animal” model be similarly informative for animal distress situations (Niemi 2006)? For example, could progress in human psychopharmacology enable the extrapolation of new drugs or indications to prevent or relieve distress in laboratory animals?

  • It is essential to continue the review of currently approved euthanasia methods, discussion of the duration of an animal’s distress before loss of consciousness, and research on the applicability of the Three Rs. For example, what refinements in the euthanasia of large populations of animals (e.g., mice) would be nondistressing to the animal as well as cost-effective and safe? The use of high concentrations of carbon dioxide is similarly contentious, as it is perceived by some as likely to be painful while it is also clearly aversive. As a euthanasia agent it may also be distressful even though consciousness probably ceases in less than a minute. Furthermore, debate has focused on the use of cervical dislocation, decapitation, and neck cutting as more appropriate methods of euthanasia with respect to the time needed for the animal to lose consciousness (Hawkins et al. 2006; EFSA 2006; AVMA 2007). Last, scientific interventions should also address the serious emotional effects on personnel who habitually perform euthanasia.

  • Are there established parameters for a truly optimal husbandry system for each species of laboratory animal and for the genetic lines within those species? Animal care facility managers may wonder, for example, if it is more humane to disturb mice that normally sleep in the daytime for daily health assessments versus observ-



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