step of the process. Both the PHS Policy and the AWRs permit a great deal of flexibility in their application to research by allowing the IACUC to grant exceptions to their recommendations when acceptable justification is provided. Thus, the PHS Policy states:

The AWRs state:

A common exception to the AWRs and to the PHS Policy surgical requirements that IACUCs allow is to permit major surgery to be performed in a modified laboratory setting when necessary equipment (such as electrophysiologic recording equipment) cannot be moved to a dedicated surgical suite (see section on “Asepsis and Physical Environment,” below).

One area of confusion for IACUCs, veterinarians, and researchers alike is the definition of what actually constitutes a major surgery. Neuroscience research often involves procedures that do not meet the strict definitions of major survival surgery given in the Guide and AWRs. Some procedures do not involve both penetration and exposure of a body cavity (for example, endoscopic surgery), or they do not penetrate or expose a body cavity at all (for example intravenous infusion or injection of neuroactive or neurotoxic substances, closed-head trauma, or peripheral neurectomy). Determining whether such procedures meet the definitions of major survival surgery hinges on whether they seem likely to produce “substantial impairment of physical or physiological functions” (NRC, 1996, pp. 11-12, 61) or “permanent impairment of physical or physiological functions” (AWR 1.1).

The IACUC must assess whether a proposed minimally invasive procedure seems likely to result in an impairment of physical or physiologic functions that is substantial or permanent. If so, the procedure must be categorized as a major surgical procedure and reviewed as such by the IACUC to ensure compliance with the provisions of the Guide and the AWRs. However, both the Guide and the AWRs expect the IACUC to exercise professional judgment in applying their criteria to the review of surgical protocols. For example, the Guide does not define what constitutes a “substantial impairment of physical or physiologic functions,” and does not require that an induced impairment be permanent to be considered major surgery. The AWRs stipulate that a noninvasive procedure should result in a “permanent” impairment to be classified as major surgery, but

Front Matter (R1-R14)

Introduction (1-4)

1 Regulatory and Ethical Considerations (5-11)

2 Protocol-Development Strategies (12-29)

3 General Animal-Care Concerns (30-68)

4 Survival Studies (69-87)

5 Prolonged Nonsurvival Studies (88-93)

6 Studies of Neural Injury and Disease (94-101)

7 Perinatal Studies (102-108)

8 Agents and Treatments (109-122)

9 Behavioral Studies (123-149)

References (150-174)

Appendix A: Sample Size Determination (175-180)

Appendix B: Estimating Animal Numbers (181-190)

Appendix C: Biographical Sketches of Authoring Committee (191-194)

Index (195-209)