Animal reduction techniques offer a variety of partial solutions to the enduring controversial issue of animal use in scientific research. In the United States alone, The Humane Society estimates that over 50 million animals are used in experiments annually.
Institutions must submit annual reports to the U.S. Department of Agriculture regarding the usage of some laboratory animals, such as nonhuman primates and rabbits. Conversely, animals such as fish, mice, and rats have no government agency reporting requirements.
When methods such as animal reduction are introduced, the number of laboratory animals in usage can be reduced, and experiments can be intentionally designed to protect their welfare.
The Three Rs, Refinement, Replacement, and Reduction, have become a standard ethical framework for addressing the welfare of laboratory animals.
Refinement refers to a range of approaches that decrease the suffering of research animals, improving their welfare from the start of the experiment to the finish. Russell and Burch wrote that “refinement might be regarded as an art or an ability to improvise.”
Methods of refinement may include providing proper housing for research animals and diminishing their distress by training them properly for participation as well as administering pain-minimizing treatments.
Replacement pertains to approaches that replace the use of animals in research. Russell and Burch separated this technique into two modes: relative replacement and absolute replacement.
Relative replacement still utilizes animals in research, but they are not subjected to any distress throughout the course of the experiment. For example, researchers may use anesthetized subjects to perform biological assays.
Absolute replacement completely eliminates the use of animals, removing them from any stage of research. Russell and Burch noted that “absolute replacement may be regarded as the absolute ideal.”
Reduction indicates methods that reduce the number of animals used in research while still obtaining comparable experimental outcomes.
As the authors best put it, “desirable as replacement is, it would be a mistake to put all our humanitarian eggs in this basket alone.” Russell and Burch make a point to highlight the importance of animal reduction, dubbing it a gradual process. Even small steps regarding animal reduction can bring about improvements in laboratory animal welfare.
On top of the time considerations and cost of using animals in research, the resulting experimental data does not always translate well to human application. Alternatively, advance research strategizing can be used as an animal reduction technique that may ultimately lead to more efficient results.
Norecopa, Norway’s Three Rs advancement platform, created a set of experiment planning directives that consider laboratory animal welfare with support from the RSPCA of England and Wales.
The Planning Research and Experimental Procedures on Animals: Recommendations for Excellence (PREPARE) guidelines suggest multiple ethical considerations, such as addressing the Three Rs, performing harm-benefit assessments, and defining measurable and humane endpoints.
Another set of guidelines, Animal Research: Reporting of In Vivo Experiments (ARRIVE), provides scaffolding to help maximize research outcomes and report data for the benefit of others.
Sharing research data and resources, including the animals themselves, is another animal reduction technique. By designing better experiments from the planning stages, fewer animals can be used in a more efficient manner.
When data is correctly reported and shared, the redundancy of repeatedly running the same experiments at various research institutions is reduced.
Improved experimental design can also result in animal reduction. For example, instead of treating animal models at random, intentionally selecting animals with a specific spread of characteristics can result in fewer animals needed for the experiment overall.
Statistical analysis prior to the start of an experiment can generate more accurate results. Less data is needed to obtain a target level of accuracy.
When the Three Rs are discarded in research, unnecessary animal suffering is intensified. Despite the lack of need to report the treatment of rats, mice, and other specimens under the Animal Welfare Act, their well-being still contributes to experimental results.
There are multiple methods of improving animal welfare during research, such as cage cleaning and environmental enrichment. Some animal models, such as zebrafish, require more complex environments than a laboratory may provide by default. Making modifications, such as adding physical structures or dietary variety, can improve their quality of life throughout the course of experiments.
This being said, animal reduction decreases the need to rely solely on animal models in the first place. It can reduce the total animal populations needed without compromising their quality of life or the robustness of the final experimental data.
The advancing technological landscape of the bioscience world provides multiple additional methods for animal reduction in scientific research.
Blind trial and error methodologies are rendered more obsolete as scalable mechanistic models and platforms that increase preclinical insight become widely accessible.
In June 2022, a bill was passed by the U.S. House of Representatives that amended a section of the Federal Food, Drug, and Cosmetic Act, allowing novel alternatives to animal testing in the drug development process. Nonclinical tests can now include computer modeling, cell-based assays, microphysiological systems and organ chips, and various nonhuman or biology-based test methods in addition to animal tests.
As stated above, animal testing data doesn’t always have clinical translatability. A publication by Alacrita, “Replacing the Surrogates: Beyond In Vivo Preclinical Models,” notes that animal models are incapable of representing the full spectrum of human disease. Relying on animal testing by default is not always the most efficient way to approach each unique research process.
The publication points out that Artificial Intelligence is one area with recent advances that contribute to the animal reduction conversation. “Interestingly, VeriSIM Life is developing digital animal simulations to potentially circumvent the need for animal testing - or at least to provide early predictive read outs and reduce animal testing requirements as part of screening.”
2D renderings of induced pluripotent stem cell (iPSC) assays have been used in areas such as toxicology testing, and 3D organoids can directly show a drug’s effect on parts of the body. Organ-on-a-chip technology is even further advanced, and demonstrates how a drug affects the interconnected organs of the body in turn.
These organ interconnections can be digitally modeled, as well. Mechanistic modeling can mathematically predict a drug’s absorption and effect throughout the human system, likewise resulting in animal reduction.
Above all, animal reduction techniques can reduce experiment time and cost investments, contribute to better research planning, and offset the ethical burden of laboratory animal welfare.
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