Although we will presently focus on animal models, biomedical research makes and has made use of a large variety of experimental subjects and preparations ranging from human volunteers and laboratory animals through embryos, isolated organs, tissues, and cells from humans as well as animals. Experimental materials have also included bacteria, fungi, and protozoa, and artificial materials are increasingly being used in the more recent physical, chemical, and computer modeling. In biomedical science, animal subjects or materials derived from animals are commonly used to construct animal models, which serve to imitate (patho)physiological states known to occur in target species (usually man but sometimes other species as well). Animal models of such states allow the experimental study of the condition to a degree often impossible in human subjects.

The use of animal models has had a tremendous impact on medical progress. Several internationally collaborating organizations provide objective information about the use of animals in medical research: Understanding Animal Research (UK), Americans for Medical Progress (USA), National Association for Biomedical Research (USA), and European Coalition for Biomedical Research (EU). Several surveys have documented the importance of animal research in general to the advancement of human and veterinary medicine. The almost exponential growth of biomedical knowledge has coincided historically with the introduction of research on animal subjects. The website of AnimalResearchInfo.com (1) provides a nice timeline illustrating the developments in medicine since the end of the nineteenth ­century, transforming healthcare, extending and improving the quality of life of millions, based on vital animal (model) experimentation. Nicoll and Russell e.g. (2) found that animal experimentation contributed to almost three quarters of all important biomedical advances between 1901 and 1975. Animal research plays a crucial role in scientists’ understanding of diseases and in the development of effective medical treatments. AnimalResearchInfo.com (1) lists those disorders and diseases, which are now prevented or cured with the knowledge obtained through animal experimentation. The value of animal experimentation in the advances of human health is further exemplified by the list of Nobel prizes awarded for Physiology or Medicine. Since the beginning of the twentieth century, these prizes have charted the world’s greatest medical advances. Of the 98 Nobel Prizes awarded for Physiology or Medicine up to 2008, 79 were directly dependent on animal-based research, or the discovery relied on crucial data obtained from animal studies by other research groups (1,3).

The physiological system of the classic Greek physician Claudius Galenus (130–201) was based on a blend of Ancient Greek philosophy and some rather haphazard anatomical observation. The humoral doctrine (red blood, yellow and black bile, phleghm) was adopted from Hippocrates (460–377 BC). All matter was supposed to consist of a mixture of the elements fire, water, air, and earth, and the qualities hot, wet, cold, and dry, and came to live through the action of three varieties of pneuma (spiritus animalis, spiritus vitalis, and spiritus naturalis). Diseases and their treatments were construed according to this medical and physiological system, which endured largely unchanged for almost 15 centuries. The distinguished British physician William Harvey (1578–1657), although trained in the Galenic tradition, was forced to overthrow the system based on the dissection of human cadavers and various animals, and some simple vivisectional observations (4). His Exercitatio anatomica de motu cordis et sanguinis in animalibus (1628) provides the first description of blood circulation. He proved his theory on the pathway of blood flow experimentally, and showed that blood is impelled mechanically by a “pump-like” heart. Harvey opened up new avenues in scientific enquiry, and established the use of animals in physiology. Another famous pioneer, the French philosopher René Descartes (1596–1650) was the first author to attempt to explain all bodily functions according to purely mechanical laws. Descartes grounded his work on observation, including some animal experiments, but he was limited by his speculative physiological conceptions and inadequate anatomical knowledge.

The use of animal models in the experimental study of the nervous system dates back at least 300 years (5). The Dutch scientist Jan Swammerdam (1637–1680) probably conducted the first experiment in electrophysiology by showing that he could make a frog’s leg wrapped in silver wire contract when it touched a copper ring. Almost 100 years later, Luigi Galvani (1737–1798) found that muscles in a frog’s legs contracted in unison with intermittent production of electricity. Galvani devised many ways to generate electricity and study its effects on excitable tissues in a series of experiments leading to what then became known as the concept of animal electricity. Although the insights of later workers were required to put Galvani’s observations in the right perspective, Galvani was without doubt one of the founders of electrophysiology. The frog still is an important experimental animal in the study of the functions of the nervous system.

During the end of the nineteenth and the beginning of the twentieth century, the rate of medical progress accelerated dramatically. Major discoveries of decisive significance to humanity were made in which the use of research animals again played a vital role. Louis Pasteur (1822–1895) used, of course, animals in his seminal work on pathogenic agents and vaccination. Pioneering bacteriologists like Robert Koch (1843–1910) often used mice to identify the pathogenic organisms they studied (6). The work on these animal models of infectious disease not only helped to identify the pathogenic agents of devastating diseases like anthrax, cholera, or tuberculosis, but were crucial for screening and evaluation of various antibacterial agents. Koch’s former assistant Paul Ehrlich (1854–1915) and coworkers infected rabbits with syphilis, and used them to prove the efficacy of arsenical substances against this disease. However, Ehrlich’s dream to find chemical substances with special affinity for pathogenic organisms, or “magic bullets” as he called them, was really made reality through the work of Gerhard Domagk (1895–1964). Domagk found that mice treated with the sulfonamide preparation Prontosil survived injections with hemolytic streptococci, which were shown to be lethal in control animals. Following this first demonstration of Prontosil ’s efficacy in 1932, experiments with sulfonamide preparations were conducted everywhere, eventually leading to the therapeutic application of Prontosil and its derivatives, and the treatment of several previously fatal diseases. The work of Domagk marked the beginning of a new era in biomedical science. It demonstrated that diseases could be treated effectively by means of chemical compounds, but incidentally, it also showed the importance of animals in medical research. Domagk used infected mice rather than bacterial cultures to investigate the antibacterial effects of a series of substances. He thus showed that Prontosil, although inactive on cultured germs, did display clear-cut antibacterial effects in vivo through its active sulfonamide metabolite.