The use of animals in biomedical research59silenced most of them (6, 28). The British Cruelty toAnimals Act, introduced in 1976, balanced the rivalclaims and animal lovers receded into backgrounduntil 1970, when a utilitarian philosopher PeterSinger started to advocate the rights of animals andgenerally opposed the use of animals in biomedicalresearch (2, 28). Other important contemporary proponentsof animal rights, but with slightly differentviews consistent more with deontological theory areTom Reagan and Christopher D. Stone, who believethat animals have inherent rights (6, 28). There areseveral philosophical viewpoints that attempt toexplain the moral status of animals, but all thesemajor theories and their derivatives are subjectto several objections. Classical utilitarianism, forexample, has often been used to justify the use ofanimals in biomedical research, by making the argumentthat the benefits gained (e.g. developmentof vaccines for deadly diseases) from using animalsoutweighs the pain and suffering that animals mustendure (6). On the other hand, as Singer says, thisdoctrine promotes equality, therefore all living beingsare equal, so to count human suffering andignoring animal suffering violates this rule (29, 30).Clearly, the present debate over animal use in research,testing and education is marked by differentexplanations of philosophical doctrines, differentreligious views and ethics based arguments (6, 27,31). Only a few philosophers have lent their voices toresearchers. One of them, Michael A. Fox, author ofThe Case for Animal Experomentation (University ofCalifornia Press, 1986), was later convinced by thecritics and became an advocate for animal rights(28). Other supporters of research noted that natureis cruel (cats play with mice, etc.), that humans eatanimal meet, raise animals for food and that evolutionhas placed us on top, so it is natural for us touse other creatures (28, 31).Nonetheless, a substantial majority of scientistsbelieve that the use of laboratory animals is justifiablefor the benefit of humankind (health, knowledgeand safety), but they should be treated as humaneas possible and they should not be suffering. Therange of public and scientific opinions on the rightsand wrongs of using animals in research is broadand is based on philosophical and religious views(6). On one side there is the liberty of humans to useanimals for important research (knowledge, healthand safety) and on the other side, a moral dilemmathat animals are free beings and that we have norights over them (6). To date, these questions remainedunsolved. Scientists have been justifyingthe use of animals by stating that it is necessaryfor maintaining human and animal health, protectionof the environment, and that in the absence ofhuman data, animal research is the most reliablemeans for estimating the risks of new compounds(6, 8). On the other side, the growing number of animalprotection groups throughout the world voicedconsiderable opposition to the use of whole animalsfor scientific purposes and even some scientistswere skeptical: they stressed that our understandingof human cancer and other diseases cannotbe gleaned from animal studies because geneticchanges and control seem different (4, 5, 8).Despite this, laboratory animals have been usedextensively as experimental models in virtually allfields of biomedicine (8). After the famous bill Crueltyto Animals Act in 1876, several attempts havebeen made to write laws that regulate animal rightsand welfare in science research. The book, publishedin 1959, The Principles of Humane ExperimentalTechnique marked the beginning of determiningethical issues, humane endpoints and setting thegeneral guiding principles for the use of laboratoryanimals (2, 5). In USA, the Animal Welfare Act of1966 with amendments, sets the standards for theproper care and treatment of research animals (6).In Europe, the EU Animal Welfare Directive (CouncilDirective 86/609/EEC with amendments) and theCouncil of Europe Convention ETS123 guide welfareof animals used for experimental and scientificpurposes (6, 32). The European Commission hasbeen developing animal welfare legislation for over30 years. The first Community legislation on farmanimal welfare was adopted in 1974 and concernedthe stunning of animals before slaughter. Sincethen, EU has already taken various steps to improveand supplement initial policies. Some of the mainobjectives of the Commission in the future are: tocommunicate on animal welfare in Europe andabroad, to upgrade existing minimum standards foranimal protection and welfare, to promote policy-orientatedfuture research on animal protection andwelfare, to introduce standardized animal welfareindicators, to ensure that animal keepers/ handlersas well as the general public are more involved andinformed on current standards of animal protectionand welfare, and to continue to support and initiatefurther international initiatives to raise awarenessand create a greater consensus on animal welfare(http://ec.europa.eu/index_en.htm). In Slovenia,Veterinary Administration of Republic of Sloveniaregulates the area of animal welfare with the Ani-
60 P. Hudlermal Protection Act - official consolidated text (slo.,Zakon o zaščiti živali, ZZZiv) (24). The legal foundationsfor animal rights were introduced in 1993 withthe Environmental Act (slo., Zakon o varstvu okolja)and since then it has been improved and reconciliatedwith EU legislation (25, Ur.l. RS, št. 3972006,04.04.2006). ZZZiv is part of this important EnvironmentalAct, which regulates basic principles ofprotecting the nature, responsibility of humans foranimal protection and welfare, defines the rules ofproper animal care and lays down the directions forfuture amendments and extension acts. Moreover,several other international conventions bound Sloveniain the case of parliament ratifications, amongthem are Ramsar, Bonn, Bern and Washington convention,Conventions about biological diversity andprotection of migratory animals, European conventionfor the protection of animals kept for farmingpurposes, etc. (http://ec.europa.eu/food/animal/welfare/references_en.htm).The field of animal welfare is constantly evolvingand through research, promotion of dialogueand general awareness of people that animals arenot things or our property, but equal inhabitantsof planet Earth and irreplaceable link in nature’sequilibrium European commission is trying to establishthe principle of humane treatment for allanimals and how it should be applied in differentfields of animal use (26, 32). More and more countriesare adopting this point of view, which regardsanimals as independent beings and surpasses theestablished comprehension of animals as objects,originating from Roman times (6). It is commendatorythat Slovenian Animal Protection Act regardsanimals in this way and thus we granted themstatus sui generis (Latin expression indicating anidea, an entity or a reality that cannot be includedin a wider concept; independent entity) (Ur.l. RS, št.3972006, 04.04.2006).Conclusion: pro et contraCurrently, research involving laboratory animalsis absolutely essential for maintaining humanhealth and for the development of new treatments(2, 26, 33-35). Nevertheless, the emergenceof sophisticated technologies in molecular and cellbiology has enabled the development of reliable invitro tests which could replace animal experiments(5, 6). Some scientists argue that these models lacka few critical points of multicellular systems, suchas microenvironment, cooperation of all organs inthe body and responses to different environmentalstimuli. Next, the inability to study integratedgrowth processes, biochemical and metabolic pathwaysand loss of original phenotype in immortalizedcell cultures, even more restrict their usage (6). Onthe other hand, opposing parties state argumentsagainst animal use, such as: moral and ethical issuesconcerning the animal rights, physiological,genetic and epigenetic differences between animalsand humans, which confer false positive or falsenegative results (6, 16).But for now, because the use of animals in researchis by law still justifiable, minimizing unnecessarysuffering and use of animals in laboratoriesvia the implementation of the three Rs (replacement,reduction, and refinement) are the most importantgoals researchers tend to achieve (2). Replacementrefers to using sophisticated in vitro technologieswhen possible, reduction refers to minimizing thenumber of animals used for research and testing,when this is scientifically appropriate and valid, andlastly, refinement stands for optimizing the existingexperimental protocols in a way that animals aresubjected to less pain and distress (5, 6). Debate onthese moral and ethical questions regarding animaluse in research is bound to continue, but most, ifnot all, parties agree that promoting and implementationof the three Rs is desirable, when scientistsmust use animals for research (6). For now, humanpopulation must accept that in vitro methods acttogether with in vivo (whole-animal and clinical (human))studies to advance science, develop products,drugs, treat, cure and prevent disease. However, theuse of animals must be regulated by the strictestmoral and ethical standards, and when scientificallypossible, their use should give way to in vitromethodologies.References1. Shultz LD, Ishikawa F, Greiner DL. Humanized micein translational biomedical research. Nat Rev Immunol2007; 7(2): 118-30.2. Russell WMS, Burch RL. The principles of humaneexperimental technique. London: Methuen, 1959: 238 str3. Festing MF. Is the use of animals in biomedicalresearch still necessary in 2002? Unfortunately, „yes“.Altern Lab Anim 2004; 32(Suppl 1): 733-9.4. Rand MS. Selection of animal models. 2004. : http://www.uac.arizona.edu/notes/classes/animalmodels/animalmodels04.html.