Slov Vet Res 2007; 44 (3): 55-62UDC 636.02:57.089Review PaperTHE USE OF ANIMALS IN BIOMEDICAL <strong>RESEARCH</strong>Petra HudlerFaculty of Medicine, Institute of Biochemistry, Medical Center for Molecular Biology, Vrazov trg 2, 1000 Ljubljana, SloveniaE-mail: petra.hudler@mf.uni-lj.siSummary: Throughout the history invertebrate and vertebrate models have been used in fundamental and goal-orientedscientific research to gain new information on cell and organ anatomy, mechanisms of the diseases and methods to preventthem, behavioral research, for production, development, testing of quality and safety of drugs, food, cosmetic andother products, and to answer scientific questions that would have been impossible to be gathered directly from humans.Although researchers are continually developing non-animal models, research on complex multigenic diseases and therapeuticstesting sometimes require the use of in vivo models. It is generally recognized that in the absence of human data,animal research in many cases can offer most accurate approximations and predictions of human responses.Key words: ethics, medical; animals, laboratory–experiments; research; disease models, animalIntroductionThe use of animals in scientific research and educationinevitably raises moral and ethical issues.Many studies have been done to assess the validityof alternative methods (cell lines, computer simulations,etc.), but complex biological processes andtesting of therapeutics often require in vivo analysis(1). Inarguably, humanity owns many benefits ofmodern medicine and countless advances in basicscientific knowledge to animal experimentation (2).The conflicts between the claims of science andmedicine and those of humanity in our treatmentof lower animals have undoubtedly no easy solution(3, 4). When, in the late nineteenth century, these divergentideas appeared, the British members of Parliamentintroduced the famous Cruelty to AnimalsAct (1876) that balanced the rival claims (2, 5). Therapid development of several biomedical disciplinesin the twentieth century caused an increase of animalusage (6). Nowadays, establishment of animalcare, legislation and ethical committees, which areresponsible for approval of experiments, have agreat impact on animal use and welfare.In complex diseases, finding all the mutatedgenes is vital for understanding and consequentlyReceived: 2 July 2007Accepted for publication: 27 August 2007treating multigenic disorders (1, 7). Therefore, laboratoryanimals have been used as experimentalmodels to discern biological mechanisms leadingto the development of the diseases, detection of potentialcarcinogens, testing different drugs, cancertherapeutics and consumer products, such as cosmetics,household cleaning products etc., determiningthe right doses for treatment and many more.In fact, there are no real substitutes for laboratoryanimals, although extensive research is being donein the direction of replacing them with appropriatein vitro systems (5, 8). Cell cultures, bacteria, yeastor even computer simulations can provide usefulinformation, but the complexity of multicellular organismsstill requires research and testing on animals.Cancer for example, is, in essence, a geneticdisease characterized by a pathological breakdownin the processes which control proliferation, differentiationand death of particular cells (8). The useof modern and classical molecular biology toolsrevealed many important genes, which are directlyor indirectly responsible for the genesis of variouscancers due to the accumulation of multiple geneticalterations, inheritance of susceptible alleles andenvironmental stimuli (9, 10). However, the cleargenetic basis revealing these molecular events intumor development and progression is still unclear.Much of our understanding of carcinogenesis was(and still is) obtained from the studies on estab-
56P. Hudlerlished cell lines prepared from human tumors (11).However, these cells are unable to form multicellularforms identical to those found in humans andare therefore inappropriate for studying biologicaland molecular processes underlying complex diseases.This review briefly covers the use of animal modelsin biomedical research of the diseases, mainlycancer, the benefits and limitations of laboratoryanimals and discusses ethical issues and legislation,concerning animal use.A short history of using animal modelsHumans “use” animals in several different ways.In addition to their use in research, testing and education,they are also used for food and fiber production,for sports and entertainment. Animals can alsobe kept as pets for the purpose of companionship.They are also used in virtually every field of biomedicalresearch, which covers a long list of disciplines(molecular biology, anatomy, anesthesiology,biochemistry, biomedical engineering, cell biology,dentistry, developmental biology, endocrinology,entomology, genetics, gerontology, histology, immunology,metabolism, microbiology, neurology, nutrition,oncology, parasitology, pathology, pharmacology,physiology, psychology, radiology, reproductivebiology, surgery, teratology, toxicology, veterinaryscience, virology, zoology,…), behavioral research(depression, drug addiction, aggression,…), testingof products for toxicity and for education ofstudents (medical, veterinarian, advanced life sciencesstudents) (6). Almost all medical knowledge,understanding of the structure and function oforgans, treatments and vaccines, has involved theuse of experimental animals. The ancient Egyptiansacquired basic anatomical knowledge through embalmingpractices (5). The first attempts to classifyand systematize knowledge of the natural world,although with many errors, were undertaken bythe Greeks. Galen, the Greek physician and philosopher,is believed to be among the first scientists toperform vivisections and post-mortems on animals,mostly apes and pigs (http://www.zephyrus.co.uk).He extrapolated his discoveries directly to humans,thus initiating many mistakes, which due to theprohibition of Church of post-mortem dissectionsof human body, were perpetuated well into the 16thcentury (12). In the medieval Europe, the influenceof the Church obstructed scientific research andalmost all science was based upon ancient Greekand Egyptian authorities, Aristotle, Ptolemaeus,Galen, Hippocrates, Herophilos and Erasistratos.The quest for medical discoveries continued morethan one thousand years later, when in 1543 Vesaliuspublished the first complete textbook of humananatomy, De Humanis Corporis Fabrica (12). Hestudied medicine and through dissecting the humancorpses he discovered the Galen’s errors. He isconsidered as a beginner of modern medicine andwas succeeded by William Harvey whose book Onthe motion of the heart and blood (1628) revealed thebasic mechanisms of these two organs (5). His explanationof blood system led to a more extensive use ofanimals in Europe (5). In 1865, French physiologistClaude Bernard published a book Introduction tostudy of experimental medicine, which advocatedthe chemical and physical induction of disease inexperimental models (13). Next, the discovery of severaltypes of anaesthesia in the 19th century (ether,nitrous oxide, chloroform, cocaine and its derivatives)also promoted the use of laboratory animals(14). The increasing use of experimental animalsin the 19th and 20th century was not universallyapplauded, but the works of Louis Pasteur, RobertKoch and many others on developing vaccines anddiscerning the mechanisms of diseases, such ascholera and tuberculosis, advocated and justifiedthe use of »animal models« (5).The concept of animal models in biomedicalresearchDespite the widespread use of human cancer-derivedcell lines, their limitations sometimes compelthe scientists to use animal models (15). The termanimal model is loosely defined as: “An animal witha disease either the same as or like a disease inhumans. Animal models are used to study the developmentand progression of diseases and to testnew treatments before they are given to humans.Animals with transplanted human cancers or othertissues are called xenograft models” (NCI Dictionaryof Cancer Terms).The researchers use different animal models tostudy the molecular mechanisms, the cause andcure of human disorders (4). According to Rand theymay be conveniently classified into five groups (4):1. Induced (experimental) disease models2. Spontaneous (genetic) disease models3. Transgenic disease models4. Negative disease models5. Orphan disease models