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Model organism

From Wikipedia, the free encyclopedia
(Redirected fromMouse model)
Organisms used to study biology across species
Escherichia coli is agram-negativeprokaryotic model organism
Drosophila melanogaster, one of the most famous subjects forgenetics experiments
Saccharomyces cerevisiae, one of the most intensively studiedeukaryotic model organisms inmolecular andcell biology

Amodel organism is anon-humanspecies that is extensively studied to understand particularbiological phenomena, with the expectation that discoveries made in themodel organism will provide insight into the workings of other organisms.[1][2] Model organisms are widely used to research humandisease whenhuman experimentation would be unfeasible orunethical.[3] This strategy is made possible by thecommon descent of all living organisms, and the conservation ofmetabolic anddevelopmental pathways andgenetic material over the course ofevolution.[4]

Research using animal models has been central to most of the achievements of modern medicine.[5][6][7] It has contributed most of the basic knowledge in fields such as humanphysiology andbiochemistry, and has played significant roles in fields such asneuroscience andinfectious disease.[8][9] The results have included the near-eradication of polio and the development oforgan transplantation, and have benefited both humans and animals.[5][10] From 1910 to 1927,Thomas Hunt Morgan's work with the fruit flyDrosophila melanogaster identifiedchromosomes as the vector of inheritance for genes,[11][12] andEric Kandel wrote that Morgan's discoveries "helped transform biology into an experimental science".[13] Research in model organisms led to further medical advances, such as the production of thediphtheria antitoxin[14][15] and the 1922 discovery ofinsulin[16] and its use in treating diabetes, which had previously meant death.[17] Modern general anaesthetics such ashalothane were also developed through studies on model organisms, and are necessary for modern, complex surgical operations.[18] Other 20th-century medical advances and treatments that relied on research performed in animals includeorgan transplant techniques,[19][20][21][22] the heart-lung machine,[23]antibiotics,[24][25][26] and thewhooping cough vaccine.[27]

In researching humandisease, model organisms allow for better understanding the disease process without the added risk of harming an actual human. The species of the model organism is usually chosen so that it reacts to disease or its treatment in a way that resembles humanphysiology, even though care must be taken when generalizing from one organism to another.[28] However, many drugs, treatments and cures for human diseases are developed in part with the guidance of animal models.[29][30] Treatments for animal diseases have also been developed, including forrabies,[31]anthrax,[31]glanders,[31]feline immunodeficiency virus (FIV),[32]tuberculosis,[31] Texas cattle fever,[31]classical swine fever (hog cholera),[31]heartworm, and otherparasitic infections.[33] Animal experimentation continues to be required for biomedical research,[34] and is used with the aim of solving medical problems such as Alzheimer's disease,[35] AIDS,[36] multiple sclerosis,[37] spinal cord injury, many headaches,[38] and other conditions in which there is no usefulin vitro model system available.

Model organisms are drawn from all threedomains of life, as well asviruses. One of the first model systems formolecular biology was the bacteriumEscherichia coli (E. coli), a common constituent of the human digestive system. The mouse (Mus musculus) has been used extensively as a model organism and is associated with many important biological discoveries of the 20th and 21st centuries.[39] Other examples include baker's yeast (Saccharomyces cerevisiae), theT4 phage virus, thefruit flyDrosophila melanogaster, the flowering plantArabidopsis thaliana, andguinea pigs (Cavia porcellus). Several of the bacterial viruses (bacteriophage) that infectE. coli also have been very useful for the study of gene structure andgene regulation (e.g. phagesLambda andT4).[40] Disease models are divided into three categories: homologous animals have the same causes, symptoms and treatment options as would humans who have the same disease, isomorphic animals share the same symptoms and treatments, and predictive models are similar to a particular human disease in only a couple of aspects, but are useful in isolating and making predictions about mechanisms of a set of disease features.[41]

History

[edit]

The use of animals in research dates back toancient Greece, withAristotle (384–322 BCE) andErasistratus (304–258 BCE) among the first to perform experiments on living animals.[42] Discoveries in the 18th and 19th centuries includedAntoine Lavoisier's use of aguinea pig in acalorimeter to prove thatrespiration was a form of combustion, andLouis Pasteur's demonstration of thegerm theory of disease in the 1880s usinganthrax in sheep.[43]

Research using animal models has been central to most of the achievements of modern medicine.[5][6][7] It has contributed most of the basic knowledge in fields such as humanphysiology andbiochemistry, and has played significant roles in fields such asneuroscience andinfectious disease.[8][9] For example, the results have included the near-eradication of polio and the development oforgan transplantation, and have benefited both humans and animals.[5][10] From 1910 to 1927,Thomas Hunt Morgan's work with the fruit flyDrosophila melanogaster identifiedchromosomes as the vector of inheritance for genes.[11][12]Drosophila became one of the first, and for some time the most widely used, model organisms,[44] andEric Kandel wrote that Morgan's discoveries "helped transform biology into an experimental science".[13]D. melanogaster remains one of the most widely used eukaryotic model organisms. During the same time period, studies on mouse genetics in the laboratory ofWilliam Ernest Castle in collaboration withAbbie Lathrop led to generation of the DBA ("dilute, brown and non-agouti") inbred mouse strain and the systematic generation of other inbred strains.[45][46] The mouse has since been used extensively as a model organism and is associated with many important biological discoveries of the 20th and 21st centuries.[39]

In the late 19th century,Emil von Behring isolated thediphtheria toxin and demonstrated its effects in guinea pigs. He went on to develop an antitoxin against diphtheria in animals and then in humans, which resulted in the modern methods of immunization and largely ended diphtheria as a threatening disease.[14] The diphtheria antitoxin is famously commemorated in the Iditarod race, which is modeled after the delivery of antitoxin in the1925 serum run to Nome. The success of animal studies in producing the diphtheria antitoxin has also been attributed as a cause for the decline of the early 20th-century opposition to animal research in the United States.[15]

Subsequent research in model organisms led to further medical advances, such asFrederick Banting's research in dogs, which determined that the isolates of pancreatic secretion could be used to treat dogs withdiabetes. This led to the 1922 discovery ofinsulin (withJohn Macleod)[16] and its use in treating diabetes, which had previously meant death.[17]John Cade's research in guinea pigs discovered the anticonvulsant properties of lithium salts,[47] which revolutionized the treatment ofbipolar disorder, replacing the previous treatments of lobotomy or electroconvulsive therapy. Modern general anaesthetics, such ashalothane and related compounds, were also developed through studies on model organisms, and are necessary for modern, complex surgical operations.[18][48]

In the 1940s,Jonas Salk used rhesus monkey studies to isolate the most virulent forms of thepolio virus,[49] which led to his creation of apolio vaccine. The vaccine, which was made publicly available in 1955, reduced the incidence of polio 15-fold in the United States over the following five years.[50]Albert Sabin improved the vaccine by passing the polio virus through animal hosts, including monkeys; the Sabin vaccine was produced for mass consumption in 1963, and had virtually eradicated polio in the United States by 1965.[51] It has been estimated that developing and producing the vaccines required the use of 100,000 rhesus monkeys, with 65 doses of vaccine produced from each monkey. Sabin wrote in 1992, "Without the use of animals and human beings, it would have been impossible to acquire the important knowledge needed to prevent much suffering and premature death not only among humans, but also among animals."[52]

Other 20th-century medical advances and treatments that relied on research performed in animals includeorgan transplant techniques,[19][20][21][22] the heart-lung machine,[23]antibiotics,[24][25][26] and thewhooping cough vaccine.[27] Treatments for animal diseases have also been developed, including forrabies,[31]anthrax,[31]glanders,[31]feline immunodeficiency virus (FIV),[32]tuberculosis,[31] Texas cattle fever,[31]classical swine fever (hog cholera),[31]heartworm, and otherparasitic infections.[33] Animal experimentation continues to be required for biomedical research,[34] and is used with the aim of solving medical problems such as Alzheimer's disease,[35] AIDS,[36][53][54] multiple sclerosis,[37] spinal cord injury, many headaches,[38] and other conditions in which there is no usefulin vitro model system available.

Selection

[edit]

Models are those organisms with a wealth of biological data that make them attractive to study as examples for otherspecies and/or natural phenomena that are more difficult to study directly. Continual research on these organisms focuses on a wide variety of experimental techniques and goals from many different levels of biology—fromecology,behavior andbiomechanics, down to the tiny functional scale of individualtissues,organelles andproteins. Inquiries about the DNA of organisms are classed asgenetic models (with short generation times, such as thefruitfly andnematode worm),experimental models, andgenomic parsimony models, investigating pivotal position in the evolutionary tree.[55] Historically, model organisms include a handful of species with extensive genomic research data, such as the NIH model organisms.[56]

Often, model organisms are chosen on the basis that they are amenable to experimental manipulation. This usually will include characteristics such as shortlife-cycle, techniques for genetic manipulation (inbred strains,stem cell lines, and methods oftransformation) and non-specialist living requirements. Sometimes, the genome arrangement facilitates the sequencing of the model organism's genome, for example, by being very compact or having a low proportion ofjunk DNA (e.g.yeast,arabidopsis, orpufferfish).[57]

When researchers look for an organism to use in their studies, they look for several traits. Among these are size,generation time, accessibility, manipulation, genetics, conservation of mechanisms, and potential economic benefit. As comparativemolecular biology has become more common, some researchers have sought model organisms from a wider assortment oflineages on thetree of life.

Phylogeny and genetic relatedness

[edit]

The primary reason for the use of model organisms in research is the evolutionary principle that all organisms share some degree of relatedness and genetic similarity due tocommon ancestry. The study of taxonomic human relatives, then, can provide a great deal of information about mechanism and disease within the human body that can be useful in medicine.[citation needed]

Various phylogenetic trees for vertebrates have been constructed using comparativeproteomics, genetics, genomics as well as the geochemical and fossil record.[58] These estimations tell us that humans and chimpanzees last shared a common ancestor about 6 million years ago (mya). As our closest relatives, chimpanzees have a lot of potential to tell us about mechanisms of disease (and what genes may be responsible for human intelligence). However, chimpanzees are rarely used in research and are protected from highly invasive procedures. Rodents are the most common animal models. Phylogenetic trees estimate that humans and rodents last shared a common ancestor ~80-100mya.[59][60] Despite this distant split, humans and rodents have far more similarities than they do differences. This is due to the relative stability of large portions of the genome, making the use of vertebrate animals particularly productive.[citation needed]

Genomic data is used to make close comparisons between species and determine relatedness. Humans share about 99% of their genome with chimpanzees[61][62] (98.7% with bonobos)[63] and over 90% with the mouse.[60] With so much of the genome conserved across species, it is relatively impressive that the differences between humans and mice can be accounted for in approximately six thousand genes (of ~30,000 total). Scientists have been able to take advantage of these similarities in generating experimental and predictive models of human disease.[citation needed]

Use

[edit]

There are many model organisms. One of the first model systems formolecular biology was the bacteriumEscherichia coli, a common constituent of the human digestive system. Several of the bacterial viruses (bacteriophage) that infectE. coli also have been very useful for the study of gene structure andgene regulation (e.g. phagesLambda andT4). However, it is debated whether bacteriophages should be classified as organisms, because they lack metabolism and depend on functions of the host cells for propagation.[64]

Ineukaryotes, several yeasts, particularlySaccharomyces cerevisiae ("baker's" or "budding" yeast), have been widely used ingenetics andcell biology, largely because they are quick and easy to grow. Thecell cycle in a simpleyeast is very similar to the cell cycle inhumans and is regulated byhomologous proteins. The fruit flyDrosophila melanogaster is studied, again, because it is easy to grow for an animal, has various visible congenital traits and has apolytene (giant) chromosome in its salivary glands that can be examined under a light microscope. TheroundwormCaenorhabditis elegans is studied because it has very defined development patterns involving fixed numbers of cells, and it can be rapidly assayed for abnormalities.[65]

Disease models

[edit]
Main article:Animal disease model

Animal models serving in research may have an existing, inbred or induceddisease or injury that is similar to a human condition. These test conditions are often termed asanimal models of disease. The use of animal models allows researchers to investigate disease states in ways which would be inaccessible in a human patient, performing procedures on the non-human animal that imply a level of harm that would not be considered ethical to inflict on a human.

The best models of disease are similar inetiology (mechanism of cause) and phenotype (signs and symptoms) to the human equivalent. However complex human diseases can often be better understood in a simplified system in which individual parts of the disease process are isolated and examined. For instance, behavioral analogues ofanxiety orpain in laboratory animals can be used to screen and test newdrugs for the treatment of these conditions in humans. A 2000 study found that animal models concorded (coincided on true positives and false negatives) with human toxicity in 71% of cases, with 63% for nonrodents alone and 43% for rodents alone.[66]

In 1987, Davidson et al. suggested that selection of an animal model for research be based on nine considerations. These include

1) appropriateness as an analog, 2) transferability of information, 3) genetic uniformity of organisms, where applicable, 4) background knowledge of biological properties, 5) cost and availability, 6) generalizability of the results, 7) ease of and adaptability to experimental manipulation, 8) ecological consequences, and 9) ethical implications.[67]

Animal models can be classified as homologous, isomorphic or predictive. Animal models can also be more broadly classified into four categories: 1) experimental, 2) spontaneous, 3) negative, 4) orphan.[68]

Experimental models are most common. These refer to models of disease that resemble human conditions in phenotype or response to treatment but are induced artificially in the laboratory. Some examples include:

Spontaneous models refer to diseases that are analogous to human conditions that occur naturally in the animal being studied. These models are rare, but informative. Negative models essentially refer to control animals, which are useful for validating an experimental result. Orphan models refer to diseases for which there is no human analog and occur exclusively in the species studied.[68]

The increase in knowledge of thegenomes of non-humanprimates and othermammals that are genetically close to humans is allowing the production ofgenetically engineered animal tissues, organs and even animal species which express human diseases, providing a more robust model of human diseases in an animal model.

Animal models observed in the sciences ofpsychology andsociology are often termedanimal models of behavior. It is difficult to build an animal model that perfectly reproduces thesymptoms of depression in patients. Depression, as othermental disorders, consists ofendophenotypes[83] that can be reproduced independently and evaluated in animals. An ideal animal model offers an opportunity to understandmolecular,genetic andepigenetic factors that may lead to depression. By using animal models, the underlying molecular alterations and the causal relationship betweengenetic or environmental alterations and depression can be examined, which would afford a better insight intopathology of depression. In addition,animal models of depression are indispensable for identifying noveltherapies for depression.[84][85]

Important model organisms

[edit]
See also:List of model organisms

Model organisms are drawn from all threedomains of life, as well asviruses. The most widely studiedprokaryotic model organism isEscherichia coli (E. coli), which has been intensively investigated for over 60 years. It is a common,gram-negative gut bacterium which can be grown and cultured easily and inexpensively in a laboratory setting. It is the most widely used organism inmolecular genetics, and is an important species in the fields ofbiotechnology andmicrobiology, where it has served as thehost organism for the majority of work withrecombinant DNA.[86]

Simple modeleukaryotes include baker's yeast (Saccharomyces cerevisiae) and fission yeast (Schizosaccharomyces pombe), both of which share many characters with higher cells, including those of humans. For instance, manycell division genes that are critical for the development ofcancer have been discovered in yeast.Chlamydomonas reinhardtii, a unicellulargreen alga with well-studied genetics, is used to studyphotosynthesis andmotility.C. reinhardtii has many known and mapped mutants and expressed sequence tags, and there are advanced methods for genetic transformation and selection of genes.[87]Dictyostelium discoideum is used inmolecular biology andgenetics, and is studied as an example ofcell communication,differentiation, andprogrammed cell death.

Laboratory mice, widely used in medical research

Among invertebrates, thefruit flyDrosophila melanogaster is famous as the subject of genetics experiments byThomas Hunt Morgan and others. They are easily raised in the lab, with rapid generations, highfecundity, fewchromosomes, and easily induced observable mutations.[88] ThenematodeCaenorhabditis elegans is used for understanding the genetic control of development and physiology. It was first proposed as a model for neuronal development bySydney Brenner in 1963, and has been extensively used in many different contexts since then.[89][90]C. elegans was the first multicellular organism whose genome was completely sequenced, and as of 2012, the only organism to have itsconnectome (neuronal "wiring diagram") completed.[91][92]

Arabidopsis thaliana is currently the most popular model plant. Its small stature and short generation time facilitates rapid genetic studies,[93] and many phenotypic and biochemical mutants have been mapped.[93]A. thaliana was the first plant to have itsgenomesequenced.[93]

Amongvertebrates,guinea pigs (Cavia porcellus) were used byRobert Koch and other early bacteriologists as a host for bacterial infections, becoming a byword for "laboratory animal", but are less commonly used today. The classic model vertebrate is currently the mouse (Mus musculus). Many inbred strains exist, as well as lines selected for particular traits, often of medical interest, e.g. body size, obesity, muscularity, and voluntarywheel-running behavior.[94]The rat (Rattus norvegicus) is particularly useful as a toxicology model, and as a neurological model and source of primary cell cultures, owing to the larger size of organs and suborganellar structures relative to the mouse, while eggs and embryos fromXenopus tropicalis andXenopus laevis (African clawed frog) are used in developmental biology, cell biology, toxicology, and neuroscience.[95][96] Likewise, thezebrafish (Danio rerio) has a nearly transparent body during early development, which provides unique visual access to the animal's internal anatomy during this time period. Zebrafish are used to study development, toxicology and toxicopathology,[97] specific gene function and roles of signaling pathways.

Other important model organisms and some of their uses include:T4 phage (viral infection),Tetrahymena thermophila (intracellular processes),maize (transposons),hydras (regeneration andmorphogenesis),[98]cats (neurophysiology),chickens (development),dogs (respiratory and cardiovascular systems),Nothobranchius furzeri (aging),[99] non-human primates such as therhesus macaque andchimpanzee (hepatitis,HIV,Parkinson's disease,cognition, andvaccines), andferrets (SARS-CoV-2)[100]

Selected model organisms

[edit]

The organisms below have become model organisms because they facilitate the study of certain characters or because of their genetic accessibility. For example,E. coli was one of the first organisms for which genetic techniques such astransformation orgenetic manipulation has been developed.

Thegenomes of all model species have beensequenced, including theirmitochondrial/chloroplast genomes.Model organism databases exist to provide researchers with a portal from which to download sequences (DNA, RNA, or protein) or to access functional information on specific genes, for example the sub-cellular localization of the gene product or its physiological role.

Model OrganismCommon nameInformal classificationUsage (examples)
VirusPhi X 174ΦX174Virusevolution[101]
ProkaryotesEscherichia coliE. coliBacteriabacterial genetics, metabolism
Pseudomonas fluorescensP. fluorescensBacteriaevolution, adaptive radiation[102]
Eukaryotes, unicellularDictyostelium discoideumAmoebaimmunology, host–pathogen interactions[103]
Saccharomyces cerevisiaeBrewer's yeast
Baker's yeast
Yeastcell division, organelles, etc.
Schizosaccharomyces pombeFission yeastYeastcell cycle, cytokinesis, chromosome biology, telomeres, DNA metabolism, cytoskeleton organization, industrial applications[104][105]
Chlamydomonas reinhardtiiAlgaehydrogen production[106]
Tetrahymena thermophila,T. pyriformisCiliateeducation,[107] biomedical research[108]
Emiliania huxleyiPlanktonsurface sea temperature[109]
PlantsArabidopsis thalianaThale cressFlowering plantpopulation genetics[110]
Physcomitrella patensSpreading earthmossMossmolecular farming[111]
Populus trichocarpaBalsam poplarTreedrought tolerance, lignin biosynthesis, wood formation, plant biology, morphology, genetics, and ecology[112]
Animals, nonvertebrateCaenorhabditis elegansNematode, RoundwormWormdifferentiation, development
Drosophila melanogasterFruit flyInsectdevelopmental biology, human brain degenerative disease[113][114]
Callosobruchus maculatusCowpea WeevilInsectdevelopmental biology
Animals, vertebrateDanio rerioZebrafishFishembryonic development
Fundulus heteroclitusMummichogFisheffect of hormones on behavior
Nothobranchius furzeriTurquoise killifishFishaging, disease, evolution
Oryzias latipesJapanese rice fishFishfish biology, sex determination[115]
Anolis carolinensisCarolina anoleReptilereptile biology, evolution
Mus musculusHouse mouseMammaldisease model for humans
Gallus gallusRed junglefowlBirdembryological development and organogenesis
Taeniopygia castanotisAustralian zebra finchBirdvocal learning, neurobiology[116]
Xenopus laevis
Xenopus tropicalis[117]
African clawed frog
Western clawed frog
Amphibianembryonic development

Limitations

[edit]

Many animal models serving as test subjects in biomedical research, such as rats and mice, may be selectivelysedentary,obese andglucose intolerant. This may confound their use to model human metabolic processes and diseases as these can be affected by dietary energy intake andexercise.[118] Similarly, there are differences between the immune systems of model organisms and humans that lead to significantly altered responses to stimuli,[119][120][121] although the underlying principles of genome function may be the same.[121] The impoverished environments inside standard laboratory cages deny research animals of the mental and physical challenges are necessary for healthy emotional development.[122] Without day-to-day variety, risks and rewards, and complex environments, some have argued that animal models are irrelevant models of human experience.[123]

Mice differ from humans in several immune properties: mice are more resistant to sometoxins than humans; have a lower totalneutrophil fraction in theblood, a lowerneutrophilenzymatic capacity, lower activity of thecomplement system, and a different set ofpentraxins involved in theinflammatory process; and lack genes for important components of the immune system, such asIL-8,IL-37,TLR10,ICAM-3, etc.[76] Laboratory mice reared inspecific-pathogen-free (SPF) conditions usually have a rather immature immune system with a deficit ofmemory T cells. These mice may have limited diversity of themicrobiota, which directly affects the immune system and the development of pathological conditions. Moreover, persistent virus infections (for example,herpesviruses) are activated in humans, but not inSPF mice, withseptic complications and may change the resistance to bacterialcoinfections. “Dirty” mice are possibly better suitable for mimicking human pathologies. In addition, inbred mouse strains are used in the overwhelming majority of studies, while thehuman population is heterogeneous, pointing to the importance of studies in interstrain hybrid,outbred, and nonlinear mice.[76]

Unintended bias

[edit]

Some studies suggests that inadequate published data in animal testing may result in irreproducible research, with missing details about how experiments are done omitted from published papers or differences in testing that may introduce bias. Examples of hidden bias include a 2014 study fromMcGill University inMontreal, Canada which suggests that mice handled by men rather than women showed higher stress levels.[124][125][126] Another study in 2016 suggested that gutmicrobiomes in mice may have an impact upon scientific research.[127]

Alternatives

[edit]

Ethical concerns, as well as the cost, maintenance and relative inefficiency of animal research has encouraged development of alternative methods for the study of disease. Cell culture, orin vitro studies, provide an alternative that preserves the physiology of the living cell, but does not require the sacrifice of an animal for mechanistic studies. Human, induciblepluripotent stem cells can[citation needed] also elucidate new mechanisms for understanding cancer and cell regeneration. Imaging studies (such as MRI or PET scans) enable non-invasive study of human subjects. Recent advances in genetics and genomics can identify disease-associated genes, which can be targeted for therapies.

Many biomedical researchers argue that there is no substitute for a living organism when studying complex interactions in disease pathology or treatments.[128][129]

Ethics

[edit]

Debate about the ethical use of animals in research dates at least as far back as 1822 when the British Parliament under pressure from British and Indian intellectuals enacted the first law for animal protection preventing cruelty to cattle.[130] This was followed by theCruelty to Animals Act 1835 and theCruelty to Animals Act 1849, which criminalized ill-treating, over-driving, and torturing animals. In 1876, under pressure from theNational Anti-Vivisection Society, the Cruelty to Animals Act 1849 was amended to include regulations governing the use of animals in research. This new act stipulated that 1) experiments must be proven absolutely necessary for instruction, or to save or prolong human life; 2) animals must be properly anesthetized; and 3) animals must be killed as soon as the experiment is over. Today, these three principles are central to the laws and guidelines governing the use of animals and research. In the U.S., the Animal Welfare Act of 1970 (see alsoLaboratory Animal Welfare Act) set standards for animal use and care in research. This law is enforced by APHIS's Animal Care program.[131]

In academic settings in which NIH funding is used for animal research, institutions are governed by the NIH Office of Laboratory Animal Welfare (OLAW). At each site, OLAW guidelines and standards are upheld by a local review board called the Institutional Animal Care and Use Committee (IACUC). All laboratory experiments involving living animals are reviewed and approved by this committee. In addition to proving the potential for benefit to human health, minimization of pain and distress, and timely and humane euthanasia, experimenters must justify their protocols based on the principles of Replacement, Reduction and Refinement.[132]

"Replacement" refers to efforts to engage alternatives to animal use. This includes the use of computer models, non-living tissues and cells, and replacement of “higher-order” animals (primates and mammals) with “lower” order animals (e.g. cold-blooded animals, invertebrates) wherever possible.[133]

"Reduction" refers to efforts to minimize number of animals used during the course of an experiment, as well as prevention of unnecessary replication of previous experiments. To satisfy this requirement, mathematical calculations of statistical power are employed to determine the minimum number of animals that can be used to get a statistically significant experimental result.

"Refinement" refers to efforts to make experimental design as painless and efficient as possible in order to minimize the suffering of each animal subject.

See also

[edit]

References

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