Animal testing, also known as in vivo testing, is the practice of using live, non-human animals in experiments to answer scientific questions or determine the safety of substances. This methodology has been a standard part of scientific research, contributing to the understanding of biology and the development of medical treatments. It involves using non-human organisms as models to predict outcomes in human systems. While still used in many fields, animal testing is increasingly subject to rigorous regulation and the development of alternative approaches.
The Scope and Procedures of Animal Testing
Animal testing is broadly utilized across basic biological research, medical development, and safety evaluation, often serving as a prerequisite for human clinical trials. This research focuses on creating animal models that mimic human diseases to study pathology and test new therapies. For instance, researchers utilize genetically modified mice, such as those that carry human genes for amyloid plaques and tau tangles, to study the progression of Alzheimer’s disease.
Non-human primates, which share up to 98% of their DNA with humans, are often employed for research on complex systems like the brain and infectious diseases where rodents are not sufficiently predictive. Primate studies are relevant for developing vaccines for diseases like Zika and Ebola, or for research into neurodegenerative conditions. Mice and rats, however, remain the most commonly used animals due to their small size, rapid reproduction, and genetic similarity to humans across many protein-coding genes.
Beyond medical discovery, animals are used in toxicity and product safety testing. One traditional procedure is the Lethal Dose 50% (LD50) test, which measures the amount of a substance required to kill half of the test animals, typically rats or mice, when administered orally, by inhalation, or through skin application. The Draize test, first developed in 1944, involves applying a test substance to the eye or shaved skin of a restrained rabbit to assess irritation or corrosion over a period of up to 14 days. These toxicity tests are increasingly being modified or phased out due to concerns about animal suffering and their predictive accuracy for human outcomes.
Oversight and Legal Standards
The use of animals in research is governed by complex regulations. In the United States, the primary federal legislation is the Animal Welfare Act (AWA), which sets minimum standards for the housing, handling, and veterinary care of certain warm-blooded animals used in research, exhibition, and transport. The AWA excludes laboratory-bred rats (Rattus), mice (Mus), and birds from its definition of a protected animal, despite these species constituting the vast majority of animals used in research.
Every institution that uses regulated animals must establish an Institutional Animal Care and Use Committee (IACUC) to oversee and evaluate the animal care and use program. The IACUC reviews and approves every proposed animal research protocol to ensure compliance with federal and institutional guidelines. This committee is legally required to include:
- A veterinarian
- A scientist
- A non-scientist
- A member unaffiliated with the institution
Central to the ethical and legal framework guiding modern animal use is the principle of the “Three Rs”: Replacement, Reduction, and Refinement. Replacement requires researchers to use methods that avoid or substitute the use of animals entirely whenever scientifically feasible. Reduction focuses on minimizing the number of animals used to obtain scientifically valid data, often achieved through rigorous experimental design and statistical analysis. Refinement demands modifications to husbandry or experimental procedures to alleviate or minimize any potential pain, suffering, or distress.
Non-Animal Testing Methods
The mandate for Replacement has driven significant innovation in non-animal testing methods, often grouped under the term “New Approach Methodologies” (NAMs). One sophisticated alternative is the Organ-on-a-Chip (OOC) technology, which mimics the physiological functions of human organs. These thumb-drive-sized chips integrate microfluidic channels and three-dimensional cell cultures, allowing researchers to simulate organ-specific functions like the breathing motion of a lung or the filtering of a kidney. OOC systems are considered highly predictive because they use human cells and replicate the mechanical and biochemical environment of the body.
In silico modeling, or computer-based simulation, is another growing field that uses complex algorithms and computational chemistry to predict how a substance will interact with biological targets. By leveraging vast databases of chemical structures and biological data, researchers can conduct virtual screening of millions of compounds to assess properties like toxicity or drug efficacy before any laboratory work is performed. This method significantly reduces the number of compounds that need to be physically synthesized and tested, streamlining the discovery process and reducing reliance on traditional testing methods.
Microdosing studies provide an early, human-relevant alternative for drug development by employing human volunteers for what are known as Phase 0 trials. A microdose is an extremely small, sub-therapeutic amount of a drug—typically less than 1/100th of the dose calculated to produce a pharmacological effect. This non-toxic dose allows scientists to use ultra-sensitive techniques like Accelerator Mass Spectrometry (AMS) to track how the human body absorbs, distributes, metabolizes, and excretes the compound. The continued development and regulatory acceptance of these advanced methods are steadily shifting the paradigm away from animal-based research.