Better Science I. INTRODUCTION In 1959, William Russell and Rex Burch, the founders of the modern alternatives movement, published their landmark book, The Principles of Humane Experimental Technique. Their simple dictum -- "if we are to use a criterion for choosing experiments to perform, the criterion of humanity is the best we could possibly invent" - has survived decades of non-acceptance, suspicion, misunderstanding and derision to become a central principle of the emerging science of alternatives. Alternatives have progressed from being wishful thinking by a few visionary scientists and humane individuals to a mainstream approach to answering questions posed by students, those with commercial interests, and scientists. Such methods have matured from a perceived or fabricated threat to biomedical research to an obvious opportunity for advancement without the pain and distress associated with the use of animals. As Dr. Michael Balls, former Director of the European Center for the Validation of Alternative Methods (ECVAM) noted, "this is a time of non-violent revolutions, when alternatives are replacing more traditional and outdated uses of animals to protect public welfare and educate future generations of biological scientists and conduct basic biomedical research." Throughout the 19th and 20th centuries, there have not been two competing systems - one based on animal models and one derived from humane alternatives - with the animal models found to be superior. Animal experimentation today in large part results from a historical accident rather than an accumulation of successful performances. In Europe the use of animals for safety and product quality purposes has declined significantly for several decades. Unfortunately that trend may be reversed due to politically motivated calls for massive new testing programs in both Europe and the United States (i.e., High Production Volume - chemicals produced in very large quantities; Endocrine Disruptors - chemicals with potential to affect human and/or wildlife reproduction; and the Children's Health Initiative - consideration of chemical safety related to children's susceptibility). What is happening in the United States? According to the U.S. Pharmacopoeia, which describes mandatory safety tests for drugs and other pharmaceutical products, animal tests now account for less than two percent of all drug testing to ensure product quality. This is down from 11.2 percent in 1985. During the past decade, with one notable exception, the total number of animals used in the United States laboratories has declined approximately 50 percent, in large part due to the adoption and use of alternatives. This trend, however, has reversed for one group - transgenic animals, mostly rats and mice, which are denied legal protection in the United States and for whom there are no reliable statistics on numbers of animals used. In addition to elucidating the concepts of humane research and the importance of alternatives, Russell and Burch formalized the possible options into three broad categories (3Rs) that are not mutually exclusive. One or all could apply to any research or testing protocol or educational exercise. Replacement methods represent the ultimate goal of the alternatives approach to basic biomedical research, testing and education. Refinement refers to those techniques and attitudes that alleviate or eliminate pain and distress experienced by the animals utilized in laboratory procedures. This may involve environmental and/or behavioral enrichment, humane endpoints (not involving pain, distress and/or death), better veterinary care and expanded use of analgesics and anesthetics. Reduction refers to any changes that contribute to the use of fewer animals, such as better research and statistical design and elimination of duplication. Both Refinement and Reduction are best viewed as interim steps on the way to the ultimate goal of complete Replacement of all animal use (i.e., in vitro tests). Animals are traditionally utilized in four broad categories - each characterized by its own unique set of attitudes, patterns of usage, and degrees of successful application of the alternatives approach. These four areas include biomedical research; production and testing of biologicals; education; and product development and safety testing. Biomedical Research: Basic biomedical research is the largest consumer of animals worldwide and, in the United States, the group most resistant to adopting the alternatives approach to answering their research questions. One factor distinguishing this hesitant response from the more favorable reception of industry may be that the former typically involves the use of someone else's money and the latter their own in-house funding. Regardless of this history, the variety and sophistication of alternative methods, especially cell and tissue culture techniques (growing cells and tissues in various types of containers in vitro), continues to expand. The current research emphasis on embryonic and adult stem cells -- possibly the ultimate in vitro alternatives -- is the most obvious recent manifestation of this trend. Production and Testing of Biologicals: The production of biologicals, such as vaccines and antibodies, is in large part an alternatives-focused activity, with the safety testing of these products gradually switching to in vitro or physiochemical (basic chemical analysis) methods. Education: By its very nature, educational demonstrations and practice sessions, such as dissections and physiology/anatomy labs, are ideally suited for adoption of the alternatives approach. It is in this category that the development and use of replacement alternatives has been most successful. Product Development and Safety Testing: As noted by Phil Botham, Syngenta Central Toxicology Laboratory, "toxicology offers both a threat and an opportunity for reduction, refinement and replacement alternatives to animal experimentation." For logistical and economic reasons, such household product and pharmaceutical companies are motivated to develop and use alternative techniques. Rapid progress here depends, however, on regulatory authorities (i.e., the Food and Drug Administration and the Environmental Protection Agency) abstaining from instituting new testing requirements based on outmoded animal-based approaches. Although the majority of toxicological research on biological mechanisms of chemical injury is done using in vitro methods and industry has widely acknowledged the superiority of alternative methods for safety testing, resistance still remains within some national and international regulatory organizations that establish and enforce safety testing requirements. It is clear that animal-based methods currently used in toxicological testing have not provided the assurances of harm or safety needed by the public and have in fact directly contributed to the existing problems of toxic ignorance. To address these historical failings, Replacement alternatives need to integrate rational testing requirements (not the traditional check-box approach that includes all available tests regardless of relevance); maximize use of existing data in both company and government agency files; mathematical predictions; models of physiological, pharmaceutical and toxicological mechanisms; new in vitro and in silico technologies (computer and microchip); and, where appropriate, ethical uses of human volunteers, post-marketing surveillance (reporting of adverse effects of products and drugs on consumers) and epidemiology (correlations between human exposure and health effects). Development of alternative techniques is widely recognized as a legitimate and important area of basic and applied scientific investigation. Regulatory agencies in Europe and to a lesser extent in the United States are finally accepting and promoting new alternative tests that have passed vigorous scientific validation procedures. In contrast, all of the traditional animal-based safety tests were never validated and would be unlikely to pass the level of proof required of new in vitro methods. This perspective has led to an increased emphasis on the importance of new techniques as the source of scientific discovery and advancement. There is a realistic expectation that in the future the use of animals will become the infrequent, reluctant alternative.   << Back to Contents | Next Section >>

Other NEAVS Fact Sheets: Benefits of Non-Animal Tests | Xenotransplants | Animal Welfare Act | Limitations of Animal Tests | Non-Animal Product Safety Test Alternatives << Back to Better Science  | Home