Text Modified from original document by Brent Martin, DVM

As researchers attempt to avoid the use of animals, to improve the quality of their research and to utilize advances in technologies, new methods of doing research are developed. Some of these new methodologies avoid the use of animals, reduce the number of animals required to attain the intended results and lessen the impact on the animals used. These alternative methodologies should be adopted as they become available.

The use of alternative methodologies is related to the research endeavor; and therefore, a search for alternatives is as specialized as the research itself. An alternatives search cannot be described in "cookbook" fashion. There can only be a general understanding of the search goal and an informed and open mind of the investigator. No one understands the research and the objectives of each technique better than the investigator; and hence, no one is in a better position to direct the search and assess the feasibility of the potential alternatives identified than that investigator. This document is intended to provide guidance on what an alternative search is and to direct searchers to helpful resources.

• The Legal Requirements:

  • The PHS Policy:  The Public Health Service policy on humane care and use of animals requires adherence to the US Government Principles for the Utilization and Care of Vertebrate Animals used in Testing, Research, and Training. Principle III says in part "Methods such as mathematical models, computer simulation, and in vitro biological systems should be considered." Principle IV states in part that "Proper use of animals, including the avoidance or minimization of discomfort, distress, and pain when consistent with sound scientific practices, is imperative." The PHS Policy has no additional guidance on how the institution is to assure compliance with the Principles other than to hold the Animal Care Council (the IACUC) responsible for it.

  • The Federal Animal Welfare Act:   The Federal Animal Welfare Act is more specific regarding the alternatives requirement. In Subpart C, section 2.31 the USDA standards state "...the IACUC shall determine that the proposed activities or significant changes in ongoing activities meet the following requirements: .... (ii) The principal investigator has considered alternatives to procedures that may cause more than momentary or slight pain or distress to the animals, and has provided a written narrative description of the methods and sources, e.g. the Animal Welfare Information Center, used to determine that alternatives were not available." There is also a requirement in section 2.32 that the institution assure that personnel are trained in utilization of services providing information about alternatives [2.32 (c)(5)(ii)].

  • The Meaning of Alternatives:   The concepts involved in "alternatives" to animal research were originally put forth in a 1959 publication, The Principles of Humane Experimental Technique by Russell and Burch. Alternatives encompass three broad categories that are commonly called the "3 R's": replacement, reduction, and refinement. These concepts are thoroughly reviewed in Chapter 2 - Alternative Methodologies by B. Taylor Bennett in the electronic publication "Essentials for Animal Research - A Primer for Research Personnel" by Bennett, Brown and Schofield. Briefly, replacement is the use of non-animal techniques or techniques using animals that are "less sentient", reduction involves techniques to minimize the number of animals, and refinement is the use of methodologies that decrease the impact on the animals. In a 1995 article titled:  The 4th R of Research, the author argues addition of 'responsibility' to the original three R's of Russell and Burch.  Recommended for the new era of 'performance based outcomes,' the 4^th R reflects integrity, honesty, and scientific correctness in appropriate and reasonable use of laboratory animals ... parcel of which is the search for alternatives to ensure that animal life is required and necessary for biomedical advancement.
    
    

• The Search for Alternatives:

  • Defining the Goal:   The search for alternatives is not simply a literature search to show that the animal use is unique. A search for alternatives is also not a search of the literature to show that the animal use has scientific validity. Searches for unnecessary duplication and scientific validity are required; however, those searches have the wrong focus and would not be sufficient to adequately assess the possibilities for alternatives.  The alternatives search begins after the scientific validity of the use has been assured. Once the intended research results have been deemed worthy of pursuit, the focus of an alternatives search is best approached by focusing on the necessity of techniques. The techniques used in the animal research are the "causes" of potentially painful events and it is this that must be avoided or minimized. Therefore, the alternatives search is an effort to find methods of accomplishing the goals of the research with less or no animal impact.  This effort to find techniques that lessen the animal impact is clearly most important with respect to procedures that cause potential pain and distress. Pain and distress can be quite difficult to assess in animals that can not verbally describe their experiences. In practice, familiarity with normal behavior and critical observation of the animals are essential for making a reasonable appraisal of the animal's experience. More importantly in the search for alternatives, pain and distress are legally defined. Procedures that would reasonably be expected to cause pain or distress in a human if performed on a person must be considered potentially painful or distressful in other animals. The most obvious approach to reducing pain or distress is through the use of anesthetics and analgesics. However, the USDA standards define painful procedures such that the use of pain relieving drugs do not make the procedure definable as "nonpainful". Therefore, use of pain relieving drugs is a practical way of reducing the impact of the procedure on the animals but it does not change the requirement for an alternatives search.

  •  Conceptualizing the Search: The search, therefore, must focus on techniques that may cause pain. There may be several techniques used and each may need to be considered separately in the alternatives search. For instance, a research project may involve surgery to implant an aortic artery catheter and infection to induce pneumonia. These techniques are quite different and the opportunities for using alternative techniques may present themselves in entirely different places. A concurrent search for both would severely limit the search. Of further note in this example is that the surgery is unique to neither a specific species nor a specific research field. Thus the search must be designed to avoid artificial limitations such as would be imposed if "hamster" or "immunology" were search words. Techniques should be viewed as an avenue to a goal, as many techniques can be adapted to different species and research areas. For instance, the example above must consider the purpose of the catheter. If it is used to monitor blood oxygenation as an indication of disease progression, then techniques that measure this transcutaneously may be a useful alternative. In some cases, the techniques are unique to the research field. In the example, the infection procedure may be to study a specific lung infection. An alternatives search to this technique may be most appropriately done in the literature of the specific research area.

  • Conducting the Search: There are a variety of sources that can be explored for alternatives to animal research. There are a number of organizations and publications that may be helpful. Some of these are listed below. The USDA has indicated their expectation that an alternatives search includes searching a literature database. There are many literature databases available and information on useful alternatives may appear in databases quite distinct from those where the goals of the experiment would be published. Assistance with determining which databases to search and the specific search strategies for those databases is best sought from a library information specialist.
    
    

• The 4 R's of Research Alternatives:

  • Replacement techniques tend to be highly specific to the research or teaching goals; hence, they are more apt to be identified in the discipline-specific literature. These techniques are also more apt to be detected by classic "alternatives" terminology (e.g. alternatives, models, in vitro, cell culture, computer, etc.) in combination with terminology limiting the search to the research area.

  • Reduction methodologies may be developed through consultation with statisticians and experimental design specialists. This is also accomplished by careful consideration of animal disease status and genotype, appropriateness of strain or species and the quality of the animal husbandry, all to minimize experimental variation.

  • Refinement techniques are a critically important area to explore; yet, a thorough literature search for alternatives in this area is the most difficult to accomplish. This search must focus on techniques. These techniques may not be research-area specific. They may appear in reference to one species but they may be adaptable to another. The techniques must be searched considering the end result. For instance, in the example of catheter placement surgery above, a search using terminology of "surgery" or "catheter" would probably not detect the alternative possibility of using a transcutaneous oxygen monitor. Yet, this technique could completely eliminate the need for surgery.

  • Responsibility for animals:  The 4th 'R' of research is the recognition and the total acceptable of responsible searching, responsible design, responsible use, and responsible care.  The search for an alternative will, at times, be a dead end .... in simple terms, animals will be required.  In these cases, the research team proceeds with a commitment to use only those animals that will be required, and when required, they will be used with recognition of their sentience and accommodations made for the social and health needs of the animal.
    
    

• What Resources Are Available:  In searching for alternatives to animal use and for alternatives to procedures that could cause pain in animals, you should be familiar with the following resources.

  • An outgrowth of a workshop organized by the European Center for the Validation of Alternative Methods (ECVAM) and the 1996 World Congress on Alternatives has been the development of a website of "alternatives" databases. This is the most comprehensive resource on alternative methodologies available in the world.

  • NORINA is a database maintained in Norway of audiovisual resources available throughout the world. The database is the most comprehensive available and includes records of films, computer simulations, video discs, etc. NORINA is particularly useful for replacement alternatives for projects using animals in teaching.

  • The National Library of Medicine produces a bibliography of Alternatives to the Use of Live Vertebrates in Biomedical Research and Testing.

  • The Animal Welfare Information Center, AWIC, a division of the National Agricultural Library, should be contacted for assistance with both the methodology of searches as well as with assistance on seeking alternatives to specific research.
     

• References:

  • Smith, CP, AWIC tips for searching for alternatives to animal research and testing, Lab Animal, 23(3):46-48, 1994.

  • Shevell, JL and James, ML, Search for animal alternatives and the role of the information specialist, Contemporary Topics in Laboratory Animal Science, 34(3):65-68, 1995.

  • Banks RE, the 4th R of Research, Contemporary Topics in Laboratory Animal Science, 34(1):43, 1995.

  • Snow, B, Online searching for alternatives to animal testing, Online, 14:94-97, 1990.