The Aspects of the Use of Rodents in Experimental Research

Abstract

Mankind has long used animals for food, for transport and as companions. The use of animals in experimental research parallels the development of medicine, which had its roots in ancient Greece. Aristotle and Hippocrates laid down their knowledge on structure and function of the human body in their respective Historia Animalium and Corpus Hippocraticum, mainly based on dissections in animals. Galen (130–201 AD), physician of the Roman emperor Marcus Aurelius, performed physiological experiments on pigs, monkeys and dogs; these experiments provided the basis for medical practices in the centuries thereafter. After Galen, experimental science remained in a dormant stage until the beginning of the Renaissance when Vesalius popularized the empirical approach, starting with anatomical studies. Later on, physiological studies were performed as well. With the advent of Cartesian philosophy in the seventeenth century, experiments on animals could be performed without great moral problems. The French philosopher Rene Descartes (1596–1650) stated that living systems could be understood on pure mechanical principles. The difference between man and animals is that man has a mind, which is a prerequisite for awareness and consequently for the capability of feeling pain. Animals cannot think and are more like machines. However, Jeremy Bentham (1789) opposed Descartes’ views: “The question is not, can they reason? Nor, can they talk? But can they suffer?” The discovery of anesthetics and Darwin’s publication on the Origin of Species in 1859, defending the biological similarities between man and animal, contributed to an increase in animal experimentation. Claude Bernard published his book “Introduction à l’étude de la médecine expérimentale”’ in 1865, introducing methodology as a tool for the design of physiological experiments. The development of microbiology caused an increase in the use of animals, due to Koch’s ‘Postulates’ where it is stated that the pathogenicity of a microorganism can be proven after successfully infecting healthy, susceptible animals (Van Zutphen 2001). The development of biomedical disciplines such as pharmacology, toxicology and immunology caused a sharp increase in the use of animals in the twentieth century. Since the early 1980s, animal experimentation has decreased due to public awareness; strict legislation regarding animal use; the development of animal ethics committees and improved animal quality (Fig. 2.1). However, in recent decades the use of animals started to increase again, mainly due to the development of genetically modified animals, which has caused a 23 % increase in the numbers of mice used each year. This increase reflects not only the animals used in research but also the large number of mice necessary to create each genetically modified line (breeding males, donor females, vasectomized males and pseudo-pregnant recipient females). Furthermore, non-transgenic and wild-type littermates may be produced that are not suitable for research or further breeding (Dennis 2002). Genetically engineered or modified mice are those with induced mutations, including mice with: transgenes; targeted mutations (knockouts); and retroviral, proviral or chemically induced mutations. Transgenic technology focuses on the introduction or exclusion (knockout) of functional genetic material in the germ-line of an animal, thus changing the genetic characteristics of an organism and its progeny. These techniques have led to the rapid development of a variety of animal models, designed for the study of gene regulation, gene expression, pathogenesis and the treatment of human and animal diseases (e.g., Alzheimer’s disease, growth hormone disturbances, mastitis in cows, and poliovirus vaccine testing for eventual use in humans).