The use of nonhuman animal models in scientific investigation is a long-standing practice. While no single answer explains their continued prominence, the practice stems from biological requirements, regulatory expectations, and current technological shortcomings in alternative methods. Animal research models (ARMs) serve as complex, integrated biological systems that offer a level of physiological fidelity currently unattainable by other means. Their utility is primarily driven by the need to understand intricate biological processes and to ensure the safety and efficacy of new medical interventions before they reach human volunteers.
Modeling Complex Biological Systems
The primary scientific justification for using nonhuman animals is their physiological and genetic similarity to humans. Mammalian models, such as mice, share approximately 95% of their protein-coding genes with humans, making them relevant for studying the molecular basis of disease. This genetic homology means that basic cellular processes, including metabolism, reproduction, and nervous system function, operate under similar biological principles.
Studying a disease or a new drug requires a complete, functioning organism, not just isolated cells. This whole-system perspective is necessary to observe the simultaneous interaction of multiple organs, tissues, and defense mechanisms. Researchers track how a therapy is absorbed by the gut, metabolized by the liver, distributed, and eliminated by the kidneys. This complex systemic response cannot be fully replicated in simpler models.
Furthermore, understanding complex conditions like cancer or neurological disorders requires observing the complete immune response within a living host. The immune system’s intricate network determines whether a treatment is effective or causes an adverse reaction. Scientists often create genetically altered or “humanized” models, such as mice with a specific human gene, allowing for the study of human-specific diseases in a controlled environment.
Mandatory Pre-Clinical Safety Evaluation
The continued reliance on animal models is driven by the long-established process of pre-clinical safety evaluation for new medical products. Historically, regulatory bodies like the U.S. Food and Drug Administration (FDA) required extensive testing in animals to determine a drug’s toxicity profile and safe dosage range before human clinical trials. This requirement served as an ethical safeguard for human volunteers, ensuring an initial assessment of safety and efficacy was conducted in a living system.
While the FDA Modernization Act 2.0 in late 2022 lifted the mandate for animal testing, allowing alternative methods, animal models remain the default way to satisfy regulatory requirements. Drug developers must still provide comprehensive data on toxicology, pharmacokinetics, and pharmacodynamics. This testing traditionally requires using one rodent species (e.g., mouse or rat) and one non-rodent species (e.g., dog or monkey) to identify potential side effects across different physiologies.
The pre-clinical phase uses animal data to establish the No Observed Adverse Effect Level (NOAEL), which calculates the safe starting dose for Phase I human trials. Until non-animal alternatives achieve the same level of regulatory acceptance for systemic toxicity and long-term effects, whole-organism animal models remain standard practice. The underlying driver is the ethical obligation to minimize risk to human participants by thoroughly vetting a compound’s biological activity and potential harm.
Current Limitations of Non-Animal Alternatives
The need for whole-animal studies is underscored by the current limitations of non-animal alternatives, which cannot yet fully replicate the complexity of a living body. In vitro methods, such as two-dimensional cell cultures, fail to capture the three-dimensional architecture, cell-to-cell signaling, and extracellular matrix interactions found in native tissues. These simplified systems often produce results that are not predictive of a human response.
Advanced technologies like “organ-on-a-chip” systems aim to mimic organ function by culturing human cells in microfluidic devices. However, these models face challenges related to low throughput, lack of standardization, and difficulty in scaling up for mass testing. A single organ-on-a-chip cannot easily replicate the complex, long-term interplay between multiple organs necessary for understanding pharmacokinetics (absorption, metabolism, distribution, and excretion).
Modeling the adaptive immune system and its complex interactions remains a significant technical hurdle for non-animal methods. While in silico (computer modeling) approaches use vast datasets to predict outcomes, their accuracy is limited by the incomplete understanding of biological processes. The current technological gap in replicating whole-body, systemic physiology means that nonhuman animal models remain necessary for certain aspects of biomedical research and regulatory safety testing.