Model organism
[3] 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.
[13] Research in model organisms led to further medical advances, such as the production of the diphtheria antitoxin[14][15] and the 1922 discovery of insulin[16] and its use in treating diabetes, which had previously meant death.
[18] Other 20th-century medical advances and treatments that relied on research performed in animals include organ transplant techniques,[19][20][21][22] the heart-lung machine,[23] antibiotics,[24][25][26] and the whooping cough vaccine.
[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 useful in vitro model system available.
[39] 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).
[42] 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.
[11][12] Drosophila became one of the first, and for some time the most widely used, model organisms,[44] and Eric Kandel wrote that Morgan's discoveries "helped transform biology into an experimental science".
"[52] Other 20th-century medical advances and treatments that relied on research performed in animals include organ transplant techniques,[19][20][21][22] the heart-lung machine,[23] antibiotics,[24][25][26] and the whooping cough vaccine.
[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 useful in vitro model system available.
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.
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.
[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).
The fruit fly Drosophila melanogaster 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.
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.
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.
Some examples include: Spontaneous models refer to diseases that are analogous to human conditions that occur naturally in the animal being studied.
[93] 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.
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.
[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 from Xenopus tropicalis and Xenopus laevis (African clawed frog) are used in developmental biology, cell biology, toxicology, and neuroscience.
[95][96] Likewise, the zebrafish (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.
Many animal models serving as test subjects in biomedical research, such as rats and mice, may be selectively sedentary, obese and glucose intolerant.
[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.
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.
Examples of hidden bias include a 2014 study from McGill University in Montreal, Canada which suggests that mice handled by men rather than women showed higher stress levels.
[127] 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.
At each site, OLAW guidelines and standards are upheld by a local review board called the Institutional Animal Care and Use Committee (IACUC).
"Refinement" refers to efforts to make experimental design as painless and efficient as possible in order to minimize the suffering of each animal subject.
