In vivo research, commonly referred to as animal testing, is a regulated scientific practice where living organisms are used to study biological processes, assess the safety of new products, and model human diseases. The selection of a specific animal species is determined by evaluating the organism’s biological relevance, its genetic similarity to humans, and the logistical demands of the research protocol. This process ensures the chosen model provides meaningful data applicable to human or animal health. Species utilized vary widely, ranging from the most numerous laboratory animals to highly specialized subjects.
Rodents: The Primary Models
Mice and rats are the dominant subjects in biomedical research, frequently accounting for over 90% of all animals used globally. This reliance stems from biological and practical advantages that suit them for high-volume studies. Rodents share approximately 95% of their protein-coding genes with humans, allowing researchers to accurately model complex conditions like cancer, diabetes, and neurological disorders.
Their small size translates to cost-effective housing and handling, making large group sizes feasible for statistical power. Their short life cycles, typically two to three years, enable scientists to observe the full progression of chronic diseases or the effects of treatments across multiple generations quickly. Furthermore, advanced genetic manipulation techniques, such as creating “knockout” mice, have solidified their position as the foundational model for studying gene function and disease mechanisms.
Larger Mammals in Complex Studies
When the physiological simplicity of rodents cannot accurately replicate a human system, researchers turn to larger mammals whose anatomy and organ function more closely parallel our own.
Rabbits
Rabbits are frequently utilized, particularly in reproductive toxicity studies and historical acute toxicity tests, like the Draize test, which assesses ocular and dermal irritation. The rabbit eye’s lack of tear ducts means it cannot readily wash away test substances, making it a sensitive model for irritation screening.
Dogs
Dogs, most commonly Beagles, are employed due to their large size and sophisticated cardiovascular system, which is relevant for cardiac and pulmonary research. Their use is also mandated in certain drug development phases to study metabolism and pharmacokinetics, detailing how a drug is absorbed, distributed, and eliminated from the body.
Non-Human Primates (NHP)
Non-human primates (NHP), such as cynomolgus monkeys, are reserved for studies where no other species suffices. This is primarily due to their close genetic and immunological similarity to humans. NHP are indispensable in vaccine development, infectious disease research like HIV, and advanced neurological studies requiring a highly complex brain structure.
Aquatic and Avian Research Subjects
Non-mammalian vertebrates, particularly fish and birds, occupy specialized niches in research, offering unique benefits for developmental and high-throughput screening studies.
Zebrafish
The zebrafish is a rapidly rising model, prized for its external fertilization and the transparency of its embryos and larvae. This transparency permits non-invasive, real-time visualization of organ development, disease progression, and the effects of test compounds at a cellular level. Zebrafish share a high degree of genetic homology with humans, making them suitable for modeling human genetic disorders and for large-scale drug toxicity screens.
Avian Models
In avian research, fertilized chicken embryos are used extensively in virology and immunology, particularly in the production of certain human vaccines. The embryo provides a sterile, self-contained environment where viruses can be grown and manipulated to create the necessary components for immunization.
Scientific and Regulatory Reasons for Selection
The decision to use any animal model is governed by scientific necessity, logistical considerations, and external regulatory requirements.
Scientific Drivers
The primary scientific driver is biological homology—the similarity between the animal’s biological systems and those of humans—ensuring the data generated is predictive and relevant. Using genetically uniform or inbred strains, especially in rodents, minimizes biological variability necessary for achieving statistically powerful and reproducible results.
Logistical and Regulatory Factors
Logistical factors, such as reproductive rate, maintenance cost, and ease of handling, influence the choice, favoring models that can be housed efficiently and produce results quickly. Regulatory bodies, such as the U.S. Food and Drug Administration (FDA), often mandate the use of specific mammalian species for safety and efficacy testing before a new drug enters human clinical trials.
Ethical Considerations
The overarching ethical principle guiding model selection is the concept of the 3Rs—Replacement, Reduction, and Refinement. This encourages scientists to use the least sentient species capable of answering the research question. This mandate has increased the use of lower-order vertebrates, like zebrafish, in early-stage screening, while simultaneously driving the search for non-animal alternatives.