Alternatives Seminar Presented to the American Association of Laboratory Animal ScientistsCurrent Concepts in Reduction, Refinement, and Replacement Alternatives in Research and TestingBy Joanne Zurlo, Ph.D. I recently had the opportunity to organize and lead a seminar entitled "Current Concepts in Reduction, Refinement, and Replacement Alternatives in Research and Testing," which took place at the 46th National Meeting of the American Association of Laboratory Animal Scientists (AALAS) in Baltimore last October. I had been approached by members of the AALAS Program Committee at last year's meeting to develop a seminar on the topic of alternatives. AALAS is an organization of persons and institutions professionally concerned with the production, care and study of laboratory animals. Virtually all visitors to CAAT's exhibit booth at the 1994 AALAS meeting indicated to us that they need more readily available information about alternatives. The main purpose of the seminar was to provide AALAS members with perspectives from different scientific groups on the development, acceptance, and utilization of alternatives as defined by the 3Rs. I began the seminar with an historical overview of the scientific discipline of the 3Rs as first described by William M.S. Russell and Rex M. Burch in their 1959 book, The Principles of Humane Experimental Technique. The rationale for my presentation was to provide the audience with an accurate definition of the word alternatives at the outset, with the intention of dispelling current misperceptions that the word alternatives refers only to replacement rather than to all 3Rs (Reduction, Refinement, and Replacement). Dr. William Stokes, who is a CAAT advisory board member and the Associate Director for Animals and Alternative Resources at the National Institute of Environmental Health Sciences (NIEHS), spoke about recent U.S. legislation related to alternatives and activities currently underway. The NIH Revitalization Act, passed in 1993, directs the NIEHS to develop and validate alternative methods for acute and chronic safety testing as well as to establish criteria and processes for the validation and regulatory acceptance of alternative testing methods. Dr. Stokes discussed several programs instituted by NIEHS to meet these directives, including grant awards of $1.5 million/year for three years in the area of mechanistically-based alternative methods. It was evident from Dr. Stokes' presentation that NIH has responded to the legislative mandate, but in order for the discipline of alternatives to advance, it is clear that the NIH must be a visible leader in promoting the 3Rs. A very valuable practical aspect of alternatives was addressed by D'Anna Jensen of the Animal Welfare Information Center (AWIC) of the National Agricultural Library. Investigators are required by their Institutional Animal Care and Use Committee (IACUCs) to state whether alternatives exist for the animal experiments they are proposing. Many investigators do not know how to locate some information. Ms. Jensen demonstrated some of the search strategies used by information specialists at AWIC. She emphasized that the National Agricultural Library maintains access to a wide range of databases from which to search. Upon request, an AWIC representative will assist scientists in either planning a search strategy for a particular area of interest, or will actually conduct the search and mail the bibliography to the investigator. The last two speakers in the session discussed the effects of the shift toward alternatives on academic and industrial scientists. Dr. John Strandberg, Director of Comparative Medicine at the Johns Hopkins School of Medicine, presented his perspectives on some of the challenges posed to academic IACUCs. Many academic investigators who use animal models in their research do so because the vast amount of the relevant available information is based on these models, and since the nature of reseach involves adding new knowledge to a foundation of existing knowledge, there is little scientific incentive to look for a replacement alternative method. However, as Dr. Strandberg pointed out, the proper use of statistics when designing animal experiments can result in the reduction of animals used. Another important factor affecting an investigator's ability to consider alternative methods is the paucity of available information in the scientific literature directly focused on alternatives (reduction, refinement, or replacement) as such. This apparent lack of information emphasizes the tremendous value of AWIC and their information services as discussed by Ms. Jensen. Dr. DeWayne Walker, Manager of Laboratory Animal Services in the Life Sciences Sector of the 3M Company, discussed the ongoing implementation of alternatives in various segments of industry with respect to product development and safety testing. An important consideration when evaluating the response of industry to the public demand for less animal testing, is the nature of industry itself. While it has been possible to significantly reduce the number of animals for cosmetic testing, progress has been much slower for other types of products. The reason for this is that cosmetics are primarily applied to the skin, while other products are accidentally (e.g. household products) or intentionally (e.g. pharmaceuticals) ingested. However, as Dr. Walker pointed out, many alternatives are being employed to screen new products. These include replacement alternatives such as cell culture or computer modeling for detecting highly toxic agents, and reduction and refinement alternatives such as the approximate lethal dose test or the up and down procedure for assessing acute toxicity. The final class of industrial products discussed by Dr. Walker is medical devices. The industry has employed many refinement alternatives in testing implanted materials that are less invasive than previous tests. There is, however, a strong need to research non-animal methods for assessing biocompatibility. Lastly, Dr. Walker emphasized the need for continued efforts by industry to pursue the development and validation of alternative methods, particularly because of the restrictive legislation that has been passed in the European Union that will have a significant impact on American industrial practices in the future. Dr. Zurlo is Associate Director of CAAT. | 
