Many questions in the field of laboratory animal distress remain unanswered. The Committee, therefore, offers the following suggestions for research directions that can improve our understanding of distress:

  • determine whether there are biomarkers of distress that may be easily measured;

  • use genomic and proteomic technologies to study the physiology and pathophysiology of stress and distress;

  • develop possible distress predictors to be used as outcomes scores (i.e., to predict severity in clinical outcomes, mortality, etc., and adopt humane or surrogate endpoints) for laboratory animals, similar to the predictive severity scoring system used in human intensive care units;

  • delineate the mechanisms of possible associations between stress/distress and disease behaviors or abnormal behaviors (e.g., stereotypies);

  • study the influence of an organism’s characteristics (e.g., gender, age, or genetic makeup) on the development of distress;

  • identify refinements in euthanasia methods;

  • study the potential use of historical controls in appropriate research protocols;

  • determine parameters for optimal husbandry conditions for laboratory animals; and

  • determine the appropriateness of experimental designs currently used for human research in studies that depend on laboratory animal models.

The Committee also provides the following recommendations:

  1. The Three Rs (refinement, reduction, and replacement) should be the standard for identifying, modifying, avoiding, and minimizing most causes of distress in laboratory animals. While research on distress and methods of alleviating distress (e.g., the development of anesthesia or analgesia) may unavoidably cause animal suffering, the optimum goal of research and veterinary teams should be to reduce and alleviate distress in laboratory animals to the minimum necessary to achieve the scientific objective.

  2. Protocols should include efforts to improve housing and husbandry conditions through the judicious employment of strategies for enrichment, animal training, and socialization. Well-trained,

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