Scientific research frequently relies on living organisms, known as animal models, to study biological systems and understand disease progression in a complex, whole-organism setting. While in vitro (cell culture) and computational methods are continually advancing, they often cannot fully replicate the sophisticated interactions that occur within a living system, particularly for conditions like infectious diseases or neurological disorders. Using animals allows researchers to test hypotheses, identify potential drug toxicities, and establish a foundational understanding of biological processes before new therapies can be considered for human trials. The selection of a specific animal model is a deliberate choice based on its physiological and genetic relevance to the human condition being studied.
The Standard: Mice and Rats
The vast majority of animals utilized in biomedical research are rodents, primarily mice (Mus musculus) and rats (Rattus norvegicus), which account for approximately 95% of all warm-blooded laboratory animals. This preference stems from a combination of biological and practical advantages. Biologically, mice share about 95% of their protein-coding genes with humans, making them robust models for studying many human diseases, including cancer, obesity, and genetic disorders.
Rodents also offer practical benefits. Their small size makes them easier and less expensive to house and maintain. Their short life cycle is a major advantage, as a mouse has a relatively short lifespan of two to three years, allowing scientists to study multiple generations in a condensed timeframe. This rapid turnover is invaluable for understanding age-related diseases and the inheritance patterns of genetic conditions.
The most significant scientific advantage lies in the advanced genetic tools available for these species. Researchers can easily manipulate the mouse genome to create specialized models, such as transgenic mice that carry an extra gene or knockout mice where a specific gene is intentionally disabled. These genetically engineered rodents are essential for simulating human genetic disorders and investigating gene function. Rats are often the preferred model over mice for studies that require a larger animal for surgical procedures or specialized testing, such as cardiovascular research, where their larger size offers a technical advantage.
Models for Complex Physiology: Larger Mammals
When the complexity of human organ structure, body size, or cognitive function exceeds the capacity of rodent models, researchers turn to larger mammals. Non-human primates (NHPs) are often selected for studies requiring close anatomical, physiological, and genetic similarity to humans, particularly in neuroscience, infectious disease research like vaccine development, and psychological studies. Their sophisticated brains and immune systems make them relevant models for understanding complex human-specific conditions.
Pigs represent another important large animal model, offering distinct advantages for studies involving the cardiovascular system, skin, and surgical techniques. Pigs share similarities with humans in terms of organ size, metabolic profile, and skin structure, making them models for transplantation research and assessing wound healing. Historically, dogs have been used extensively in cardiovascular, orthopedic, and respiratory research, where their larger body size facilitates the development and testing of prosthetic devices and surgical methods. Other mammals, such as rabbits, are sometimes used for their unique lipid metabolic profiles and immune responses, making them suitable for modeling cardiovascular and immune-related diseases.
Essential Non-Mammalian Models
Non-mammalian models provide insights into foundational biology, offering speed and cost-efficiency for initial screening and genetic studies. The fruit fly (Drosophila melanogaster) is an invertebrate model, valued for its simple genetics, short life cycle, and prolific reproduction, which allows for rapid investigation of genetic pathways and developmental biology. Similarly, the nematode worm (Caenorhabditis elegans) is utilized, possessing a simple, entirely mapped nervous system of only 302 neurons, which makes it ideal for studying basic neurological circuits and gene variants.
The zebrafish (Danio rerio) has become a prominent vertebrate choice, especially for developmental biology and toxicology studies. Zebrafish embryos develop rapidly outside the mother and are optically transparent, allowing researchers to easily observe internal organ development and disease progression in a live, intact organism. These non-mammalian species enable the rapid, large-scale assessment of genetic variants and the screening of drug candidates.
The Framework for Use: Regulatory Standards
The use of animals in research is governed by a legal and ethical framework that dictates which animals are regulated and how they must be cared for. In the United States, the primary federal law is the Animal Welfare Act (AWA), which sets minimum standards for the housing, handling, and veterinary care of certain warm-blooded animals. The AWA covers species like dogs, cats, non-human primates, guinea pigs, and rabbits.
The AWA expressly excludes purpose-bred rats and mice of the genus Mus and Rattus, as well as birds, from its direct regulatory oversight. Although these rodents are not covered by the AWA, all research institutions receiving federal funding must still adhere to the Public Health Service (PHS) Policy, which extends humane care and use standards to all vertebrate animals. Every research facility using animals must establish an Institutional Animal Care and Use Committee (IACUC), which is responsible for reviewing and approving all experimental protocols to ensure compliance with federal, state, and institutional guidelines.