The selection of an animal model is dependent upon its genetic and physiological similarities to humans. The practice is not without controversy and there are arguments against the validity of animal models for studying human disease.
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Experimental research in human disease requires the use of controls. This means that more than one subject is required to observe the variable being tested, whilst all other factors must be kept constant.
To provide statistical validity a large sample number is required. It is therefore necessary to test on more than one subject with animal models providing a practical solution.
Preclinical treatments that utilize animal models have been found to show promising results, but often fail to achieve similar responses during human clinical trials. This makes them highly controversial.
Rodents as models for studying human disease
Rodents are the most widely utilized models in biomedical research. This is due to their genetic and physiological similarity to humans, along with the practicalities of maintenance within the laboratory.
Genetically modified mice have been particularly useful in determining gene function. A knockout mouse is a term for a mouse that has been genetically engineered to halt the activation of an existing gene.
Function can therefore be determined through observations of changes in physiology, caused by the now inactive gene. Nonetheless, rodents have proven less useful as a model for studying and treating cancer.
The majority of oncology drugs that proved successful in treating tumors within rodents fail to have the same response in humans, with most tested therapeutics never reaching the marketplace.Though rodents and humans are phylogenetically related, the difference in networks linking genes within the two species is prominent enough to limit the application of rodents as animal models for studying human disease.
The use of non-human primate models
Non-human primates provide the closest model to humans in terms of genetics and physiology. They are an important component of biomedical research that has led to greater understanding of disease development along with the formation of vaccines and treatments.
Non-human primates are often used in the final stage of pharmaceutical testing before human clinical trials commence. An example of the successful application of non-human primate models can be found in their contribution to AIDs research.
Infection of simian immunodeficiency virus (SIV) in macaques and other non-human primates produced a model that closely resembled HIV infection and AIDS in humans. Important developments including the production of a combinatorial antiretroviral treatment that can control the infection were produced from efficacy and safety trials utilizing non-human primates.
In addition, comparative research on the variety of retroviruses within the primate order has led to an enhanced comprehension of human immunology.
Improving the use of animal models
Advances in molecular biology have led to an increased number of potential drug targets, but the success rate of drugs that reach the clinical development stage remains low. This is thought to partially be caused by a higher number of drugs tested on less validated candidates.
Increased success rates rely on animal models being selected at the early stages of testing that accurately reflect the validity of a target within humans. The animal models do not have to perfectly reflect the entire disease pathway or treatment that occurs in a human, but instead form a model of a specific aspect to be tested.
Practical strategies for improving the use of animal models for studying human disease include designing human clinical trials that replicate the conditions that were tested for in the animal model. Modeling factors such as age, sex and comorbidities present in the human condition may also be useful for increasing the quality of translational studies.
Reviewed by Afsaneh Khetrapal Bsc (Hons)
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