Reduction, Refinement, Replacement, and Responsibility in Animal Research

We are all familiar with the 3 “R”’s, Reduction, Refinement, and Replacement, but there is a fourth “R”; that of Responsibility.  There have been many papers, seminars, suggestions and opinions on how best to accomplish and capture the true intentions of Russell and Burch when they first developed the concept of responsible use of laboratory animals with an eye toward compassion and care. It has long been known that animals that are humanely treated and well cared for give a more accurate picture of physiological data.  Animals under stress through overcrowding or substandard conditions often produce inaccurate data and therefore are not good research subjects. That is, of course, unless you are studying the effects of stress due to adverse environmental conditions. It is in all of our best interests to produce that highest level of valid and statistically sound, and accurate research data we are capable of by using our laboratory animals wisely, ethically, and humanely; never forgetting our responsibility to the scientific community, the animals, and mankind.  With this in mind, I would like to submit to you the following:

Principles of Animal Research

• Research must not be unnecessarily duplicative.
• Alternatives must be considered before animals are used.
• All procedures that will cause more than momentary pain or distress require the use of anesthetics, analgesics, or tranquilizers.
• The USDA, PHS, NIH and DLAR policies require that anyone using live animals in research be aware of their responsibilities according to the Animal Welfare Act and NIH policy.
• This requirement includes faculty, postdoctoral fellows, research technologists, and students.
• To protect the health of the animal colonies at University of Kentucky, and to comply with this requirement ALL research personnel who use live animals MUST attend an orientation provided by the Division of Laboratory Animal Resources BEFORE they begin working with animals.
• USDA/Animal Welfare Act
  • The federal law by which the USDA regulates the use of all warm-blooded vertebrates in research except poultry (birds), rats and mice bred exclusively for research, and farm animals used or intended for food or fiber.
• Public Health Service (PHS)
  • The federal agency which publishes policy for the humane care and use of laboratory animals and the operation of laboratory animal facilities.
• Office of Laboratory Animal Welfare (OLAW formerly OPRR)
  • The enforcement branch of NIH, which receives and reviews Animal Welfare Assurance Statements from institutions conducting research with animals and grants registration numbers to those institutions.
• National Institutes of Health (NIH)
  • The federal institution that provides the majority of funding for biomedical research
  • Endorsed the establishment of guidelines for the humane care and use of animals in biomedical research by the National Academy of Sciences (NAS)
  • Guidelines used as the “standard reference” for voluntary accreditation with AAALAC
• Institutional Animal Care and Use Committee
  • The committee within the institution that is responsible for overseeing animal research in the institution.
  • Approves investigator protocols
  • Consists of scientists, veterinarians, community members (those outside the institution) and advisory members
• AAALAC/International (Voluntary)  Association for the Assessment and Accreditation of Laboratory Animal Care
  • An organization that monitors compliance to the standards for accreditation of institutional laboratory animal care
  • Voluntary membership
  • Inspections by peer group every 3 years in order to continue accreditation
• IACUC approved animal use protocols ALWAYS REQUIRED regardless of
  12. the source of funding
      • intramural or extramural
  13. the source of the animals
      • purchased, obtained free, or bred in-house
  14. the number of animals used
      • pilot studies, learning techniques
• It is Essential that you READ the Protocol you will be working with
• Know what you can do as it pertains to your study
• If your study changes, you MUST amend the protocol BEFORE you can implement the changes. 
• This MUST be done for continued approval of the IACUC committee 

Literature Search

• Required Elements
• Date of search
• Databases or other sources searched
• Years covered in search
• Key words or search strategy used
• To comply with USDA and NIH requirements, the search must clearly document a good faith effort to find alternatives for painful or stressful procedures. Personal knowledge can be used, but not as your only source.
• Reduction - using the appropriate minimum numbers of animals for the study to yield statistically sound data
• Replacement - Are there viable alternatives to the use of animals
• Refinement - Minimizing stress and pain to the animals when ever and where ever possible
• As critical to the research as the conclusion itself, is the logical endpoints of the study.  These should be clearly defined and strictly adhered to.
• Death as an endpoint must ALWAYS be justified

USDA pain categories:

All animals listed on the IACUC approved protocol MUST be registered in one of the following categories.  It is important to note that even if the animal will be used in an acute procedure only for tissue collection, it must be entered into category C. All animals used exclusively for breeding purposes would be category B. As noted in the chart, there is no category A.

For more information, please see the USDA Pain & Distress Categories page.

Responsibility in Animal Research

The use of animals in biomedical research may be summed up in only few words, “it is a privilege, not a right”. We, in the research community have a responsibility to the animals we work with. It is our responsibility to treat these animals with respect and acknowledge and address the basic issues of humane care and thoughtful stewardship of their use. We must be ever mindful of the rules and regulations that govern the use of animals in all types of research including, behavioral, medical and psychological studies. The introduction of genetic research demands more attention be paid to the needs of genetically altered animals since the needs of these animals may have changed and so also the care it takes to maintain them.  Consequently, all of the responsibility and ethical decision making rests with us.  Everyone involved in any phase of animal research, from the daily care of the husbandry technician, the lab personnel who process the data, the investigator who designs and submits the protocol, and the member of the Institutional Animal Care and Use Committee who approves the study has an interest in the responsible, humane, and ethical care and use of our most valuable and venerable laboratory animals. We owe them a debt for their invaluable service to the advancement of science.