New and Improved Guide for the Care and Use of Laboratory Animals
By Michele Cunneen - Laboratory Animal Consultant
A revised version of The National Research Council’s Guide for the Care and Use of Laboratory Animals (the Guide) has been released as a pre-publication draft, the first revision of the Guide since 1996. The final publication date is December of this year. If only minor changes and typographical corrections are incorporated in the final edition, the 2010 version of the Guide is a step in the right direction by placing more emphasis on the quality of life for animals used in research.
Why is this document important? The Guide is the reference manual animal research programs are supposed to adhere to if they receive National Institutes of Health (NIH) money or Small Business Administration (SBA) loans, are accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC), or are located in Cambridge, Massachusetts - where a laboratory animal ordinance requires adherence to the Guide. In short, this document extends to most of the animals used in research in the United States; therefore, the changes should impact millions of animals.
Under the Guide, it is typically the responsibility of each institution to police itself, with limited direct oversight. Accountability varies, depending on the jurisdiction: NIH's Office of Laboratory Animal Welfare (OLAW) administers the program for those research projects supported by taxpayer dollars; OLAW requires an annual report and does not perform a site visit, except in some cases where there is direct evidence of noncompliance. AAALAC requires an annual report and conducts a scheduled site visit once every three years. The City of Cambridge carries out annual inspections.
The 2010 Guide appears to embody a philosophical shift from the perspective that enrichment, group housing, and social contact are "variables" that must be controlled, to an understanding that these elements can reduce stress (itself a variable) and lead to more reproducible results (better science) while improving animal welfare. Previously, the standard called for animals to be single-housed and their cages unenriched, unless you could demonstrate that group housing and enrichment would not negatively impact scientific results. The standard set in the updated Guide is that animals should be socially housed and their cages enriched. This change in emphasis should empower each institution’s Institutional Animal Care and Use Committee (IACUC)1 and animal care staff to provide enrichment and social housing as standard housing conditions. Although the 2010 Guide states that facilities "should" rather than "must" use enrichment and social housing, it is unquestionably stronger in this regard than the 1996 edition. The following is a quote from the new Guide regarding the primary enclosure:
All animals should be housed under conditions that provide sufficient space as well as supplementary structures and resources required to meet physical, physiologic, and behavioral needs. Environments that fail to meet the animals’ needs may result in abnormal brain development, physiologic dysfunction and behavioral disorders (Garner 2005; van Praag et al. 2000; Würbel 2001) that potentially compromise both animal well-being and scientific validity. The primary enclosure or space may need to be enriched to prevent such effects and improve animal well-being....
An appropriate housing space or enclosure should also account for the animals’ social needs. Social animals should be housed in stable pairs or groups of compatible individuals unless they must be housed alone for experimental reasons or because of social incompatibility.... Structural adjustments are frequently required for social housing (e.g., perches, visual barriers, refuges), and important resources (e.g., food, water, and shelter) should be provided in such a way that they cannot be monopolized by dominant animals....
The section on IACUC review of protocols is another area where the 2010 Guide emphasizes animal well-being. Previous editions of the Guide focused on IACUC review of what the project will do and what outcomes are expected. This edition has stated that the following additional items should be considered in the protocol review:
- Impact of the procedures performed on the animals’ well-being;
- Description and rationale for anticipated or selected endpoints;
- Criteria and process for timely intervention, removal of animals from a study, or euthanasia if painful or stressful outcomes are anticipated; and
- Method of euthanasia or disposition of animal, including planning for care of long-lived species following study completion.
The Guide goes on to state:
While the responsibility for scientific merit review normally lies outside the IACUC, the IACUC should evaluate scientific elements of the protocol as they relate to the welfare and use of the animals.
When considering certain animal use protocols with the potential for unrelieved pain and distress, the 2010 Guide further delineates:
...the IACUC is obliged to weigh the objectives of the study against potential animal welfare concerns. By considering opportunities for refinement, the use of appropriate non-animal alternatives and the use of fewer animals, both the institution and the Principal Investigator can begin to address their mutual obligations for humane animal care and use.
Taken together, these additions obligate the researchers to provide more detail about their projects. In some cases this will require pilot studies to obtain data they were previously not required to collect about effects on the animals. Many IACUCs, with strong institutional support, have requested and reviewed this type of information for years. However, IACUCs that were unable to get these details in the past can now ask for them irrespective of institutional support.
Many other areas of the 2010 Guide have been expanded to provide more direction to the researchers, IACUCs, and animal care staff regarding endpoints, authority to euthanize, use of Class A dealers, and the inclusion of aquatic and terrestrial animals in the discussion of housing and care.
In many research protocols, the endpoints have been ill-defined both by the regulations and by the researchers themselves. This Guide provides both a definition and a requirement for reliability:
The experimental endpoint of a study occurs when the scientific aims and objectives have been reached. The humane endpoint is the point at which pain or distress is prevented, terminated or relieved in an experimental animal. The use of humane endpoints contributes to refinement by providing an alternative to experimental endpoints that result in more severe animal pain and distress, including death. The humane endpoint should be relevant and reliable.
Prior to this edition of the Guide, it was not clear that the veterinarian was the ultimate authority in the evaluation of an ill animal. Now, there is no ambiguity:
In the case of a pressing health problem, if the responsible person (e.g., investigator) is not available or if consensus between the investigator and veterinary staff cannot be reached concerning treatment, the veterinarian must have the authority, delegated by senior administration (see Chapter 2, Institutional Official and Attending Veterinarian) and the IACUC, to treat, remove from the experiment, institute appropriate measures to relieve severe pain or distress or euthanize the animal if necessary.
While still not condemning Class B dealers, a new section titled "Animal Procurement" suggests the IACUC must approve the source and number of animals, and there is now a clear preference for Class A dealers:
...vendors of purpose-bred animals (e.g., USDA Class A dealers) regularly provide information that describes the genetic and pathogen status of their colonies or individual animals and relevant clinical history, for example, vaccination status and anthelmintic administration. Because of this, the use of purpose-bred and pre-conditioned animals is preferable when consistent with the research, teaching and testing objectives.
Zebrafish, African clawed frogs, and other non-traditional animals used in research, not considered in previous editions, are now included; definitions for care and housing of these species, as well as suggestions for design of facilities and enrichment of these species is delineated. While still general, the information starts to put these species into the professional care and use standards expected for the animals more traditionally used in research.
Overall, the 2010 Guide reflects a substantial shift towards recognizing the importance of the animal as an animal, not just another test tube in research.
1 The Institutional Animal Care and Use Committee (IACUC) is a self-regulating entity that, according to U.S. federal law, must be established by institutions that use animals for research or instructional purposes, to oversee and evaluate all aspects of the institution’s animal care and use program. For more information, see www.iacuc.org.