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117-504: For each model organism , RefSeq aims to provide separate and linked records for the genomic DNA, the gene transcripts, and the proteins arising from those transcripts. RefSeq is limited to major organisms for which sufficient data are available (121,461 distinct "named" organisms as of July 2022), while GenBank includes sequences for any organism submitted (approximately 504,000 formally described species ). RefSeq collection comprises different data types, with different origins, so it

234-523: A 2002 study has supported the protocol of precautionary administration of PEP where a child or mentally compromised individual has been alone with a bat, especially in sleep areas, where a bite or exposure may occur with the victim being unaware. Once rabies develops, death almost certainly follows. Palliative care in a hospital setting is recommended with administration of large doses of pain medication, and sedatives in preference to physical restraint. Ice fragments can be given by mouth for thirst, but there

351-460: A 2014 study from McGill University in Montreal, Canada which suggests that mice handled by men rather than women showed higher stress levels. Another study in 2016 suggested that gut microbiomes in mice may have an impact upon scientific research. Ethical concerns, as well as the cost, maintenance and relative inefficiency of animal research has encouraged development of alternative methods for

468-461: A conjugate, to bind to and allow the visualisation of rabies antigen using fluorescent microscopy techniques. Microscopic analysis of samples is the only direct method that allows for the identification of rabies virus-specific antigen in a short time and at a reduced cost, irrespective of geographical origin and status of the host. It has to be regarded as the first step in diagnostic procedures for all laboratories. Autolysed samples can, however, reduce

585-492: A few Daubenton's bats . There has been one fatal case of EBLV-2 transmission to a human. There have been four deaths from rabies, transmitted abroad by dog bites, since 2000. The last infection in the UK occurred in 1922, and the last death from indigenous rabies was in 1902. Sweden and mainland Norway have been free of rabies since 1886. Bat rabies antibodies (but not the virus) have been found in bats. On Svalbard, animals can cross

702-662: A goal of eliminating deaths from rabies by 2030. India has the highest rate of human rabies in the world, primarily because of stray dogs, whose number has greatly increased since a 2001 law forbade the killing of dogs. Effective control and treatment of rabies in India is hindered by a form of mass hysteria known as puppy pregnancy syndrome (PPS). Dog bite victims with PPS, male as well as female, become convinced that puppies are growing inside them, and often seek help from faith healers rather than medical services. An estimated 20,000 people die every year from rabies in India, more than

819-494: A larger, rabid animal, and would, therefore, not be carriers. The Virginia opossum (a marsupial, unlike the other mammals named in this paragraph, which are all eutherians / placental ), has a lower internal body temperature than the rabies virus prefers and therefore is resistant but not immune to rabies. Marsupials , along with monotremes ( platypuses and echidnas ), typically have lower body temperatures than similarly sized eutherians . In 2024, reports emerged that rabies

936-580: 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. "Replacement" refers to efforts to engage alternatives to animal use. This includes

1053-406: A lower total neutrophil fraction in the blood , a lower neutrophil enzymatic capacity, lower activity of the complement system , and a different set of pentraxins involved in the inflammatory process ; and lack genes for important components of the immune system, such as IL-8 , IL-37 , TLR10 , ICAM-3 , etc. Laboratory mice reared in specific-pathogen-free (SPF) conditions usually have

1170-547: A model for neuronal development by Sydney Brenner in 1963, and has been extensively used in many different contexts since then. C. elegans was the first multicellular organism whose genome was completely sequenced, and as of 2012, the only organism to have its connectome (neuronal "wiring diagram") completed. Arabidopsis thaliana is currently the most popular model plant. Its small stature and short generation time facilitates rapid genetic studies, and many phenotypic and biochemical mutants have been mapped. A. thaliana

1287-428: A muscle or nerve cell, the virus undergoes replication. The L protein then transcribes five mRNA strands and a positive strand of RNA all from the original negative strand RNA using free nucleotides in the cytoplasm. These five mRNA strands are then translated into their corresponding proteins (P, L, N, G and M proteins) at free ribosomes in the cytoplasm. Some proteins require post-translational modifications. For example,

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1404-666: 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, 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 and morphogenesis ), cats (neurophysiology), chickens (development), dogs (respiratory and cardiovascular systems), Nothobranchius furzeri (aging), non-human primates such as

1521-545: A person with rabies or contact with non-infectious fluid or tissue (urine, blood, feces), does not constitute an exposure and does not require post-exposure prophylaxis. But as the virus is present in sperm and vaginal secretions, it might be possible for rabies to spread through sex. There are only a small number of recorded cases of human-to-human transmission of rabies, and all occurred through organ transplants , most frequently with corneal transplantation , from infected donors. Rabies can be difficult to diagnose because, in

1638-577: A population of people in Peru with a self-reported history of one or more bites from vampire bats (commonly infected with rabies), found that out of 73 individuals reporting previous bat bites, seven people had rabies virus-neutralizing antibodies (rVNA). Since only one member of this group reported prior vaccination for rabies, the findings of the research suggest previously undocumented cases of infection and viral replication followed by an abortive infection. This could indicate that people may have an exposure to

1755-551: 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. Many animal models serving as test subjects in biomedical research, such as rats and mice, may be selectively sedentary , obese and glucose intolerant . This may confound their use to model human metabolic processes and diseases as these can be affected by dietary energy intake and exercise . Similarly, there are differences between

1872-544: A practice that has successfully reduced rabies in rural areas of Canada , France , and the United States . In Montreal , Quebec, Canada, baits are successfully used on raccoons in the Mount-Royal Park area. Vaccination campaigns may be expensive, but cost-benefit analysis suggests baits may be a cost-effective method of control. In Ontario , a dramatic drop in rabies was recorded when an aerial bait-vaccination campaign

1989-404: A protein present in the cytoplasm of nerve cells. Once the virus reaches the cell body it travels rapidly to the central nervous system (CNS), replicating in motor neurons and eventually reaching the brain. After the brain is infected, the virus travels centrifugally to the peripheral and autonomic nervous systems, eventually migrating to the salivary glands, where it is ready to be transmitted to

2106-585: A rather immature immune system with a deficit of memory T cells . These mice may have limited diversity of the microbiota , 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 in SPF mice, with septic complications and may change the resistance to bacterial coinfections . “Dirty” mice are possibly better suitable for mimicking human pathologies. In addition, inbred mouse strains are used in

2223-440: A set of symptoms in the later stages of an infection in which the person has difficulty swallowing, shows panic when presented with liquids to drink, and cannot quench their thirst. Saliva production is greatly increased, and attempts to drink, or even the intention or suggestion of drinking, may cause excruciatingly painful spasms of the muscles in the throat and larynx . Since the infected individual cannot swallow saliva and water,

2340-401: A site distant from the vaccination site. People who have previously been vaccinated against rabies do not need to receive the immunoglobulin—only the postexposure vaccinations on days 0 and 3. The side effects of modern cell-based vaccines are similar to the side effects of flu shots. The old nerve-tissue-based vaccination required multiple injections into the abdomen with a large needle but

2457-541: A teenage girl from Wisconsin , who subsequently became the first human known to have survived rabies without receiving post-exposure prophylaxis before symptom onset. Giese did require extensive rehabilitation afterward, and her balance and neural function remained impaired. The protocol has been enacted on many rabies victims since, but has been adjudged a failure; some survivors of the acute initial phase later died of rabies. Concerns have also been raised about its monetary costs and its ethics. Antiviral therapy to combat

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2574-567: A third of the global total. Australia has an official rabies-free status, although Australian bat lyssavirus (ABLV), discovered in 1996, is a rabies-causing virus related to the rabies virus prevalent in Australian native bat populations. Canine-specific rabies has been eradicated in the United States, but rabies is common among wild animals, and an average of 100 dogs become infected from other wildlife each year. High public awareness of

2691-468: A unicellular green alga with well-studied genetics, is used to study photosynthesis and motility . C. reinhardtii has many known and mapped mutants and expressed sequence tags, and there are advanced methods for genetic transformation and selection of genes. Dictyostelium discoideum is used in molecular biology and genetics , and is studied as an example of cell communication , differentiation , and programmed cell death . Among invertebrates,

2808-503: A wide variety of experimental techniques and goals from many different levels of biology—from ecology , behavior and biomechanics , down to the tiny functional scale of individual tissues , organelles and proteins . Inquiries about the DNA of organisms are classed as genetic models (with short generation times, such as the fruitfly and nematode worm), experimental models, and genomic parsimony models, investigating pivotal position in

2925-548: A wider assortment of lineages on the tree of life . 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 to common 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. Various phylogenetic trees for vertebrates have been constructed using comparative proteomics , genetics, genomics as well as

3042-412: Is Escherichia 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 in molecular genetics , and is an important species in the fields of biotechnology and microbiology , where it has served as the host organism for

3159-460: Is World Rabies Day , which promotes the information, prevention, and elimination of the disease. In Asia and in parts of the Americas and Africa, dogs remain the principal host. Mandatory vaccination of animals is less effective in rural areas. Especially in developing countries, pets may not be privately kept and their destruction may be unacceptable. Oral vaccines can be safely distributed in baits,

3276-465: Is an example of a viral pathogen modifying the behavior of its host to facilitate its transmission to other hosts. After a typical human infection by bite, the virus enters the peripheral nervous system . It then travels retrograde along the efferent nerves toward the central nervous system . During this phase, the virus cannot be easily detected within the host, and vaccination may still confer cell-mediated immunity to prevent symptomatic rabies. When

3393-455: Is classified as a neglected tropical disease . The global cost of rabies is estimated to be around US$ 8.6 billion per year including lost lives and livelihoods, medical care and associated costs, as well as uncalculated psychological trauma . The name rabies is derived from the Latin rabies , meaning "madness". The Greeks derived the word lyssa , from lud or "violent"; this root is used in

3510-439: Is difficult to build an animal model that perfectly reproduces the symptoms of depression in patients. Depression, as other mental disorders , consists of endophenotypes that can be reproduced independently and evaluated in animals. An ideal animal model offers an opportunity to understand molecular , genetic and epigenetic factors that may lead to depression. By using animal models, the underlying molecular alterations and

3627-485: Is expensive and makes up most of the cost of post-exposure treatment, ranging as high as several thousand dollars. In the UK, one dose of HRIG costs the National Health Service £1,000, although this is not flagged as a "high-cost medication". A full course of vaccine costs £120–180. As much as possible of HRIG should be injected around the bites, with the remainder being given by deep intramuscular injection at

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3744-414: Is inexpensive. It is being phased out and replaced by affordable World Health Organization intradermal-vaccination regimens. In children less than a year old, the lateral thigh is recommended. Thoroughly washing the wound as soon as possible with soap and water for approximately five minutes is effective in reducing the number of viral particles. Povidone-iodine or alcohol is then recommended to reduce

3861-511: Is necessary to establish standard categories and identifiers to store each data type. The most important categories are: For more details and more categories, see Table 1 in Chapter 18 of the book The Reference Sequence (RefSeq) Database . Several projects to improve RefSeq services are currently in development by the NCBI, often in collaboration with research centers such as EMBL-EBI: According to

3978-452: Is no good evidence intravenous hydration is of benefit. A treatment known as the Milwaukee protocol, which involves putting people with rabies symptoms into a chemically induced coma and using antiviral medications in an attempt to protect their brain until their body has had time to produce rabies antibodies, has been occasionally used. It was initially attempted in 2004 on Jeanna Giese,

4095-632: Is no substitute for a living organism when studying complex interactions in disease pathology or treatments. 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. This was followed by the Cruelty to Animals Act of 1835 and 1849, which criminalized ill-treating, over-driving, and torturing animals. In 1876, under pressure from

4212-431: Is no useful in vitro model system available. Model organisms are drawn from all three domains of life, as well as viruses . One of the first model systems for molecular biology was the bacterium Escherichia 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

4329-413: Is packed as a ribonucleoprotein complex in which RNA is tightly bound by the viral nucleoprotein. The RNA genome of the virus encodes five genes whose order is highly conserved: nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G), and the viral RNA polymerase (L). To enter cells, trimeric spikes on the exterior of the membrane of the virus interact with a specific cell receptor,

4446-420: 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 from Xenopus tropicalis and Xenopus laevis (African clawed frog) are used in developmental biology, cell biology, toxicology, and neuroscience. Likewise, the zebrafish ( Danio rerio ) has

4563-479: Is similar to a human condition. These test conditions are often termed as animal 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 in etiology (mechanism of cause) and phenotype (signs and symptoms) to

4680-471: Is spreading in South African seals, possibly making it the first outbreak documented in marine mammals . The virus is usually present in the nerves and saliva of a symptomatic rabid animal. The route of infection is usually, but not always, by a bite. In many cases, the infected animal is exceptionally aggressive, may attack without provocation, and exhibits otherwise uncharacteristic behavior. This

4797-496: Is studied, again, because it is easy to grow for an animal, has various visible congenital traits and has a polytene (giant) chromosome in its salivary glands that can be examined under a light microscope. The roundworm Caenorhabditis elegans is studied because it has very defined development patterns involving fixed numbers of cells, and it can be rapidly assayed for abnormalities. Animal models serving in research may have an existing, inbred or induced disease or injury that

RefSeq - Misplaced Pages Continue

4914-477: Is used with the aim of solving medical problems such as Alzheimer's disease, AIDS, multiple sclerosis, spinal cord injury, many headaches, and other conditions in which there is no useful in vitro model system available. Models are those organisms with a wealth of biological data that make them attractive to study as examples for other species and/or natural phenomena that are more difficult to study directly. Continual research on these organisms focuses on

5031-502: The National Anti-Vivisection Society , the Cruelty to Animals Act 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

5148-410: The fruit fly Drosophila melanogaster is famous as the subject of genetics experiments by Thomas Hunt Morgan and others. They are easily raised in the lab, with rapid generations, high fecundity , few chromosomes , and easily induced observable mutations. The nematode Caenorhabditis elegans is used for understanding the genetic control of development and physiology. It was first proposed as

5265-526: The rabies virus and Australian bat lyssavirus . Duvenhage lyssavirus may cause a rabies-like infection. The rabies virus is the type species of the Lyssavirus genus , in the family Rhabdoviridae , order Mononegavirales . Lyssavirions have helical symmetry, with a length of about 180  nm and a cross-section of about 75 nm. These virions are enveloped and have a single-stranded RNA genome with negative sense . The genetic information

5382-622: The rhesus macaque and chimpanzee ( hepatitis , HIV , Parkinson's disease , cognition , and vaccines ), and ferrets ( SARS-CoV-2 ) 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 as transformation or genetic manipulation has been developed. The genomes of all model species have been sequenced , including their mitochondrial / chloroplast genomes. Model organism databases exist to provide researchers with

5499-558: The 20th and 21st centuries. Other examples include baker's yeast ( Saccharomyces cerevisiae ), the T4 phage virus, the fruit fly Drosophila melanogaster , the flowering plant Arabidopsis thaliana , and guinea pigs ( Cavia porcellus ). Several of the bacterial viruses ( bacteriophage ) that infect E. coli also have been very useful for the study of gene structure and gene regulation (e.g. phages Lambda and T4 ). Disease models are divided into three categories: homologous animals have

5616-546: The DBA ("dilute, brown and non-agouti") inbred mouse strain and the systematic generation of other inbred strains. 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. In the late 19th century, Emil von Behring isolated the diphtheria 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

5733-465: The G protein travels through the rough endoplasmic reticulum , where it undergoes further folding, and is then transported to the Golgi apparatus , where a sugar group is added to it ( glycosylation ). When there are enough viral proteins, the viral polymerase will begin to synthesize new negative strands of RNA from the template of the positive-strand RNA. These negative strands will then form complexes with

5850-462: The N, P, L and M proteins and then travel to the inner membrane of the cell, where a G protein has embedded itself in the membrane. The G protein then coils around the N-P-L-M complex of proteins taking some of the host cell membrane with it, which will form the new outer envelope of the virus particle. The virus then buds from the cell. From the point of entry, the virus is neurotropic , traveling along

5967-491: The RefSeq release 213 (July 2022), the number of species represented in the database by counting distinct taxonomic IDs are as follows: The counts of accession and basepairs per molecule type are: Model organism A model organism is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into

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6084-559: The United States by 1965. 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." Other 20th-century medical advances and treatments that relied on research performed in animals include organ transplant techniques,

6201-439: The United States to prevent outbreaks of rabies in undomesticated animals. Immunization before exposure has been used in both human and nonhuman populations, where, as in many jurisdictions, domesticated animals are required to be vaccinated. The Missouri Department of Health and Senior Services Communicable Disease Surveillance 2007 Annual Report states the following can help reduce the risk of contracting rabies: 28 September

6318-516: The United States, 62 (70%) were attributed to bats. The most recent rabies death in the United States was in November 2021, where a Texas child was bitten by a bat in late August 2021 but his parents failed to get him treatment. He died less than three months later. Either no or very few cases of rabies are reported each year in Europe; cases are contracted both during travel and in Europe. In Switzerland

6435-430: The United States. Subsequent research in model organisms led to further medical advances, such as Frederick Banting 's research in dogs, which determined that the isolates of pancreatic secretion could be used to treat dogs with diabetes . This led to the 1922 discovery of insulin (with John Macleod ) and its use in treating diabetes, which had previously meant death. John Cade 's research in guinea pigs discovered

6552-441: The achievements of modern medicine. It has contributed most of the basic knowledge in fields such as human physiology and biochemistry , and has played significant roles in fields such as neuroscience and infectious disease . The results have included the near- eradication of polio and the development of organ transplantation , and have benefited both humans and animals. From 1910 to 1927, Thomas Hunt Morgan 's work with

6669-460: The animal from which the bite was received should also be examined for rabies. Some light microscopy techniques may also be used to diagnose rabies at a tenth of the cost of traditional fluorescence microscopy techniques, allowing identification of the disease in less-developed countries. A test for rabies, known as LN34, is easier to run on a dead animal's brain and might help determine who does and does not need post-exposure prevention. The test

6786-438: The anticonvulsant properties of lithium salts, which revolutionized the treatment of bipolar disorder , replacing the previous treatments of lobotomy or electroconvulsive therapy. Modern general anaesthetics, such as halothane and related compounds, were also developed through studies on model organisms, and are necessary for modern, complex surgical operations. In the 1940s, Jonas Salk used rhesus monkey studies to isolate

6903-457: The basic knowledge in fields such as human physiology and biochemistry , and has played significant roles in fields such as neuroscience and infectious disease . For example, the results have included the near- eradication of polio and the development of organ transplantation , and have benefited both humans and animals. From 1910 to 1927, Thomas Hunt Morgan 's work with the fruit fly Drosophila melanogaster identified chromosomes as

7020-559: The brain and meninges , symptoms can include slight or partial paralysis , anxiety , insomnia , confusion , agitation , abnormal behavior, paranoia , terror , and hallucinations . The person may also have fear of water. The symptoms eventually progress to delirium and coma . Death usually occurs two to ten days after first symptoms. Survival is almost unknown once symptoms have presented, even with intensive care. Rabies has also occasionally been referred to as hydrophobia ("fear of water") throughout its history. It refers to

7137-420: The causal relationship between genetic or environmental alterations and depression can be examined, which would afford a better insight into pathology of depression. In addition, animal models of depression are indispensable for identifying novel therapies for depression. Model organisms are drawn from all three domains of life, as well as viruses . The most widely studied prokaryotic model organism

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7254-685: The deaths occurred in Asia and Africa. As of 2015 , India (approximately 20,847), followed by China (approximately 6,000) and the Democratic Republic of the Congo (5,600), had the most cases. A 2015 collaboration between the World Health Organization, World Organization of Animal Health (OIE), Food and Agriculture Organization of the United Nation (FAO), and Global Alliance for Rabies Control has

7371-447: The disease if given within 10 days. The rabies vaccine is 100% effective if given before symptoms of rabies appear. Every year, more than 15 million people get vaccinated after potential exposure. While this works well, the cost is significant. In the US it is recommended people receive one dose of human rabies immunoglobulin (HRIG) and four doses of rabies vaccine over a 14-day period. HRIG

7488-569: The disease was virtually eliminated after scientists placed chicken heads laced with live attenuated vaccine in the Swiss Alps . Foxes, proven to be the main source of rabies in the country, ate the chicken heads and became immunized. Italy, after being declared rabies-free from 1997 to 2008, has witnessed a reemergence of the disease in wild animals in the Triveneto regions ( Trentino-Alto Adige/Südtirol , Veneto and Friuli-Venezia Giulia ) due to

7605-424: The distance the virus must travel along peripheral nerves to reach the central nervous system . Rabies is caused by lyssaviruses , including the rabies virus and Australian bat lyssavirus . It is spread when an infected animal bites or scratches a human or other animals. Saliva from an infected animal can also transmit rabies if the saliva comes into contact with the eyes, mouth, or nose. Globally, dogs are

7722-498: The early stages, it is easily confused with other diseases or even with a simple aggressive temperament. The reference method for diagnosing rabies is the fluorescent antibody test (FAT), an immunohistochemistry procedure, which is recommended by the World Health Organization (WHO). The FAT relies on the ability of a detector molecule (usually fluorescein isothiocyanate) coupled with a rabies-specific antibody, forming

7839-555: The effects of rabies has also been researched; favipiravir , for example, has shown potential at inhibiting the development of encephalitis. It has been suggested that such therapy in combination with immunotherapy and neuroprotective measures could be beneficial. Vaccination after exposure, PEP, is highly successful in preventing rabies. In unvaccinated humans, rabies is almost certainly fatal after neurological symptoms have developed. In 2010, an estimated 26,000 people died from rabies, down from 54,000 in 1990. The majority of

7956-530: The evolutionary tree. Historically, model organisms include a handful of species with extensive genomic research data, such as the NIH model organisms. Often, model organisms are chosen on the basis that they are amenable to experimental manipulation. This usually will include characteristics such as short life-cycle , techniques for genetic manipulation ( inbred strains, stem cell lines, and methods of transformation ) and non-specialist living requirements. Sometimes,

8073-455: The first to perform experiments on living animals. Discoveries in the 18th and 19th centuries included Antoine Lavoisier 's use of a guinea pig in a calorimeter to prove that respiration was a form of combustion, and Louis Pasteur 's demonstration of the germ theory of disease in the 1880s using anthrax in sheep. Research using animal models has been central to most of the achievements of modern medicine. It has contributed most of

8190-737: The fruit fly Drosophila melanogaster identified chromosomes as the vector of inheritance for genes, and Eric Kandel wrote that Morgan's discoveries "helped transform biology into an experimental science". Research in model organisms led to further medical advances, such as the production of the diphtheria antitoxin and the 1922 discovery of insulin and its use in treating diabetes, which had previously meant death. Modern general anaesthetics such as halothane were also developed through studies on model organisms, and are necessary for modern, complex surgical operations. Other 20th-century medical advances and treatments that relied on research performed in animals include organ transplant techniques,

8307-550: The genome arrangement facilitates the sequencing of the model organism's genome, for example, by being very compact or having a low proportion of junk DNA (e.g. yeast , arabidopsis , or pufferfish ). 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 comparative molecular biology has become more common, some researchers have sought model organisms from

8424-457: The genus name of the rabies virus, Lyssavirus . The period between infection and the first symptoms (incubation period) is typically one to three months in humans. This period may be as short as four days or longer than six years, depending on the location and severity of the wound and the amount of virus introduced. Initial symptoms of rabies are often nonspecific, such as fever and headache. As rabies progresses and causes inflammation of

8541-430: The geochemical and fossil record. 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

8658-563: The guidance of animal models. Treatments for animal diseases have also been developed, including for rabies , anthrax , glanders , feline immunodeficiency virus (FIV), tuberculosis , Texas cattle fever, classical swine fever (hog cholera), heartworm , and other parasitic infections . Animal experimentation continues to be required for biomedical research, and is used with the aim of solving medical problems such as Alzheimer's disease, AIDS, multiple sclerosis, spinal cord injury, many headaches, and other conditions in which there

8775-540: The heart-lung machine, antibiotics , and the whooping cough vaccine. In researching human disease , 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 human physiology , even though care must be taken when generalizing from one organism to another. However, many drugs, treatments and cures for human diseases are developed in part with

8892-428: The heart-lung machine, antibiotics , and the whooping cough vaccine. Treatments for animal diseases have also been developed, including for rabies , anthrax , glanders , feline immunodeficiency virus (FIV), tuberculosis , Texas cattle fever, classical swine fever (hog cholera), heartworm , and other parasitic infections . Animal experimentation continues to be required for biomedical research, and

9009-412: The host cells for propagation. In eukaryotes , several yeasts, particularly Saccharomyces cerevisiae ("baker's" or "budding" yeast), have been widely used in genetics and cell biology , largely because they are quick and easy to grow. The cell cycle in a simple yeast is very similar to the cell cycle in humans and is regulated by homologous proteins. The fruit fly Drosophila melanogaster

9126-904: 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 of anxiety or pain in laboratory animals can be used to screen and test new drugs 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. 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

9243-621: The immune systems of model organisms and humans that lead to significantly altered responses to stimuli, although the underlying principles of genome function may be the same. The impoverished environments inside standard laboratory cages deny research animals of the mental and physical challenges are necessary for healthy emotional development. Without day-to-day variety, risks and rewards, and complex environments, some have argued that animal models are irrelevant models of human experience. Mice differ from humans in several immune properties: mice are more resistant to some toxins than humans; have

9360-408: 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

9477-584: The laws and guidelines governing the use of animals and research. In the U.S., the Animal Welfare Act of 1970 (see also Laboratory Animal Welfare Act ) set standards for animal use and care in research. This law is enforced by APHIS's Animal Care program. 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

9594-412: The majority of work with recombinant DNA . Simple model eukaryotes 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, many cell division genes that are critical for the development of cancer have been discovered in yeast. Chlamydomonas reinhardtii ,

9711-560: 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. Rabies Rabies is a viral disease that causes encephalitis in humans and other mammals . It was historically referred to as hydrophobia ("fear of water") because its victims would panic when offered liquids to drink. Early symptoms can include fever and abnormal sensations at

9828-474: The modern methods of immunization and largely ended diphtheria as a threatening disease. The diphtheria antitoxin is famously commemorated in the Iditarod race, which is modeled after the delivery of antitoxin in the 1925 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

9945-516: The most common animal involved. In countries where dogs commonly have the disease, more than 99% of rabies cases in humans are the direct result of dog bites . In the Americas , bat bites are the most common source of rabies infections in humans, and less than 5% of cases are from dogs. Rodents are very rarely infected with rabies. The disease can be diagnosed only after the start of symptoms. Animal control and vaccination programs have decreased

10062-550: The most common animal models. Phylogenetic trees estimate that humans and rodents last shared a common ancestor ~80-100mya. 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. Genomic data is used to make close comparisons between species and determine relatedness. Humans share about 99% of their genome with chimpanzees (98.7% with bonobos) and over 90% with

10179-401: The most likely one being the acetylcholine receptor. The cellular membrane pinches in a procession known as pinocytosis and allows entry of the virus into the cell by way of an endosome . The virus then uses the acidic environment, which is necessary, of that endosome and binds to its membrane simultaneously, releasing its five proteins and single-strand RNA into the cytoplasm. Once within

10296-493: The most virulent forms of the polio virus, which led to his creation of a polio 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. 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

10413-436: The mouse. 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. There are many model organisms. One of the first model systems for molecular biology

10530-399: The mouth" effect, caused by the accumulation of saliva, is also commonly associated with rabies in the public perception and in popular culture. The remaining 20% may experience a paralytic form of rabies that is marked by muscle weakness , loss of sensation, and paralysis ; this form of rabies does not usually cause fear of water. Rabies is caused by a number of lyssaviruses including

10647-459: The neural pathways into the central nervous system . The virus usually first infects muscle cells close to the site of infection, where they are able to replicate without being 'noticed' by the host's immune system. Once enough virus has been replicated, they begin to bind to acetylcholine receptors at the neuromuscular junction. The virus then travels through the nerve cell axon via retrograde transport , as its P protein interacts with dynein ,

10764-513: The next host. All warm-blooded species, including humans, may become infected with the rabies virus and develop symptoms. Birds were first artificially infected with rabies in 1884; however, infected birds are largely, if not wholly, asymptomatic, and recover. Other bird species have been known to develop rabies antibodies , a sign of infection, after feeding on rabies-infected mammals. The virus has also adapted to grow in cells of cold-blooded vertebrates. Most animals can be infected by

10881-454: The overwhelming majority of studies, while the human population is heterogeneous, pointing to the importance of studies in interstrain hybrid, outbred , and nonlinear mice. 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

10998-422: The person receives the treatment before the start of rabies symptoms. Washing bites and scratches for 15 minutes with soap and water, povidone-iodine , or detergent may reduce the number of viral particles and may be somewhat effective at preventing transmission. As of 2016 , only fourteen people were documented to have survived a rabies infection after showing symptoms. However, research conducted in 2010 among

11115-505: The results, 7) ease of and adaptability to experimental manipulation, 8) ecological consequences, and 9) ethical implications. 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. 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

11232-405: The risk of rabies from dogs in a number of regions of the world. Immunizing people before they are exposed is recommended for those at high risk, including those who work with bats or who spend prolonged periods in areas of the world where rabies is common. In people who have been exposed to rabies, the rabies vaccine and sometimes rabies immunoglobulin are effective in preventing the disease if

11349-476: 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. The use of animals in research dates back to ancient Greece , with Aristotle (384–322 BCE) and Erasistratus (304–258 BCE) among

11466-611: The sensitivity and specificity of the FAT. The RT PCR assays proved to be a sensitive and specific tool for routine diagnostic purposes, particularly in decomposed samples or archival specimens. The diagnosis can be reliably made from brain samples taken after death. The diagnosis can also be made from saliva, urine, and cerebrospinal fluid samples, but this is not as sensitive or reliable as brain samples. Cerebral inclusion bodies called Negri bodies are 100% diagnostic for rabies infection but are found in only about 80% of cases. If possible,

11583-500: The site of exposure. These symptoms are followed by one or more of the following symptoms: nausea, vomiting, violent movements, uncontrolled excitement, fear of water, an inability to move parts of the body, confusion, and loss of consciousness . Once symptoms appear, the result is virtually always death. The time period between contracting the disease and the start of symptoms is usually one to three months but can vary from less than one week to more than one year. The time depends on

11700-469: The species studied. The increase in knowledge of the genomes of non-human primates and other mammals that are genetically close to humans is allowing the production of genetically 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 of psychology and sociology are often termed animal models of behavior . It

11817-460: The spreading of an epidemic in the Balkans that also affected Austria. An extensive wild animal vaccination campaign eliminated the virus from Italy again, and it regained the rabies-free country status in 2013, the last reported case of rabies being reported in a red fox in early 2011. The United Kingdom has been free of rabies since the early 20th century except for a rabies-like virus (EBLV-2) in

11934-581: The study of disease. Cell culture, or in 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, inducible pluripotent stem cells can 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

12051-491: 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. "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

12168-483: The vector of inheritance for genes. Drosophila became one of the first, and for some time the most widely used, model organisms, and Eric Kandel wrote that Morgan's discoveries "helped transform biology into an experimental science". D. melanogaster remains one of the most widely used eukaryotic model organisms. During the same time period, studies on mouse genetics in the laboratory of William Ernest Castle in collaboration with Abbie Lathrop led to generation of

12285-878: The virus and can transmit the disease to humans. Worldwide, about 99% of human rabies cases come from domestic dogs. Other sources of rabies in humans include bats , monkeys , raccoons , foxes , skunks , cattle , wolves , coyotes , cats , and mongooses (normally either the small Asian mongoose or the yellow mongoose). Rabies may also spread through exposure to infected bears , domestic farm animals , groundhogs , weasels , and other wild carnivorans . However, lagomorphs , such as hares and rabbits , and small rodents , such as chipmunks , gerbils , guinea pigs , hamsters , mice , rats , and squirrels , are almost never found to be infected with rabies and are not known to transmit rabies to humans. Bites from mice, rats, or squirrels rarely require rabies prevention because these rodents are typically killed by any encounter with

12402-414: The virus further. Awakening to find a bat in the room, or finding a bat in the room of a previously unattended child or mentally disabled or intoxicated person, is an indication for post-exposure prophylaxis (PEP). The recommendation for the precautionary use of PEP in bat encounters where no contact is recognized has been questioned in the medical literature, based on a cost–benefit analysis . However,

12519-399: The virus has a much higher chance of being transmitted, because it multiplies and accumulates in the salivary glands and is transmitted through biting. Hydrophobia is commonly associated with furious rabies, which affects 80% of rabies-infected people. This form of rabies causes irrational aggression in the host, which aids in the spreading of the virus through animal bites; a "foaming at

12636-576: The virus reaches the brain , it rapidly causes encephalitis , the prodromal phase, which is the beginning of the symptoms. Once the patient becomes symptomatic, treatment is almost never effective and mortality is over 99%. Rabies may also inflame the spinal cord , producing transverse myelitis . Although it is theoretically possible for rabies-infected humans to transmit it to others by biting or otherwise, no such cases have ever been documented, because infected humans are usually hospitalized and necessary precautions taken. Casual contact, such as touching

12753-639: The virus without treatment and develop natural antibodies as a result. Rabies causes about 59,000 deaths worldwide per year, about 40% of which are in children under the age of 15. More than 95% of human deaths from rabies occur in Africa and Asia. Rabies is present in more than 150 countries and on all continents but Antarctica. More than 3 billion people live in regions of the world where rabies occurs. A number of countries, including Australia and Japan, as well as much of Western Europe, do not have rabies among dogs. Many Pacific islands do not have rabies at all. It

12870-400: The virus, efforts at vaccination of domestic animals and curtailment of feral populations, and availability of postexposure prophylaxis have made rabies very rare in humans in the United States. From 1960 to 2018, a total of 125 such cases were reported in the United States; of them, 36 (28%) were attributed to dog bites suffered during international travel. Among the 89 infections acquired in

12987-420: The workings of other organisms. Model organisms are widely used to research human disease when human experimentation would be unfeasible or unethical . This strategy is made possible by the common descent of all living organisms, and the conservation of metabolic and developmental pathways and genetic material over the course of evolution . Research using animal models has been central to most of

13104-662: Was developed by the Centers for Disease Control and Prevention (CDC) in 2018. The differential diagnosis in a case of suspected human rabies may initially include any cause of encephalitis , in particular infection with viruses such as herpesviruses , enteroviruses , and arboviruses such as West Nile virus . The most important viruses to rule out are herpes simplex virus type one, varicella zoster virus , and (less commonly) enteroviruses, including coxsackieviruses , echoviruses , polioviruses , and human enteroviruses 68 to 71. New causes of viral encephalitis are also possible, as

13221-656: Was developed in 1885 by Louis Pasteur and Émile Roux . Their original vaccine was harvested from infected rabbits, from which the virus in the nerve tissue was weakened by allowing it to dry for five to ten days. Similar nerve tissue-derived vaccines are still used in some countries, as they are much cheaper than modern cell culture vaccines. The human diploid cell rabies vaccine was started in 1967. Less expensive purified chicken embryo cell vaccine and purified vero cell rabies vaccine are now available. A recombinant vaccine called V-RG has been used in Belgium, France, Germany, and

13338-450: Was evidenced by the 1999 outbreak in Malaysia of 300 cases of encephalitis with a mortality rate of 40% caused by Nipah virus , a newly recognized paramyxovirus . Likewise, well-known viruses may be introduced into new locales, as is illustrated by the outbreak of encephalitis due to West Nile virus in the eastern United States. Almost all human exposure to rabies was fatal until a vaccine

13455-440: Was launched. The number of recorded human deaths from rabies in the United States has dropped from 100 or more annually in the early 20th century to one or two per year because of widespread vaccination of domestic dogs and cats and the development of human vaccines and immunoglobulin treatments. Most deaths now result from bat bites, which may go unnoticed by the victim and hence untreated. Treatment after exposure can prevent

13572-417: Was the bacterium Escherichia coli , a common constituent of the human digestive system. Several of the bacterial viruses ( bacteriophage ) that infect E. coli also have been very useful for the study of gene structure and gene regulation (e.g. phages Lambda and T4 ). However, it is debated whether bacteriophages should be classified as organisms, because they lack metabolism and depend on functions of

13689-569: Was the first plant to have its genome sequenced . Among vertebrates , guinea pigs ( Cavia porcellus ) were used by Robert 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 voluntary wheel-running behavior. The rat ( Rattus norvegicus )

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