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 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 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 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, 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 the guidance of animal models. Treatments for animal diseases have also been developed, including for rabies, anthrax, glanders, feline immunodeficiency virus, tuberculosis, Texas cattle fever, classical swine fever, 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 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, a common constituent of the human digestive system. The protist T. brucei has become a model organism. The mouse has been used extensively as a model organism and is associated with many important biological discoveries of the 20th and 21st centuries. Other examples include baker's yeast, the T4 phage virus, the fruit fly Drosophila melanogaster, the flowering plant Arabidopsis thaliana, and guinea pigs. Several of the bacterial viruses that infect E. coli also have been very useful for the study of gene structure and gene regulation. 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.
History
The use of animals in research dates back to ancient Greece, with Aristotle and Erasistratus among 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 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 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 the DBA 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 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 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 and its use in treating diabetes, which had previously meant death. John Cade's research in guinea pigs discovered 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 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 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, 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, tuberculosis, Texas cattle fever, classical swine fever, 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 is no useful in vitro model system available.
Selection
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 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, experimental models, and genomic parsimony models, investigating pivotal position in 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 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 of junk DNA.
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 a wider assortment of lineages on the tree of life.