The Multifactorial Role of the 3Rs in Shifting the Harm-Benefit Analysis in Animal Models of Disease

Testing on animals for biomedical research is viewed as unethical by many animal advocates. The use of animals within the field is generally governed by a patchwork of state-level and national regulations, as well as a loose set of principles called the “3 Rs” (that stand for replacement, reduction, and refinement). This paper looks at the role of the 3 Rs in the promotion of ethical practices in animal experimentation, taking the view that the consistent application of the 3 Rs can result in animal research that is ethically sound.

When it comes to the use of animals in biomedical research, there is a delicate balance between what society perceives as “the good” that results from animal experiments, and the ethical distaste many have for the experiments themselves, often considered torturous to animals. In the U.S. there are various laws governing the use of animals in research, and, “underpinning this legislation is the consensus that animal experiments deserve major ethical consideration and such considerations should be in balance with the moral consideration of humans.” The balance of these factors (known more colloquially as utilitarianism) is said to be a concern of the scientific community, and that unease is often suppressed through the application of the “3 Rs”: the principle of replacement, reduction, and refinement. Since the earliest articulation of the 3 Rs in 1959, the principle has been a driving force in the utilitarian view of the use of animals in experiments. This paper, written by supporters of the 3 Rs, aims to show “how expertly designed 3 Rs methods not only reduce harms to animals but can also expand our understanding of disease and strengthen scientific outcomes to accelerate translation to the clinic to benefit patients.”

Even though the paper is generally in favor of the 3 Rs, the researchers note that “animals in biomedical research often are not in a normal state, but rather in a disease state relevant to the model or study interventions. Because the state of disease generally violates the ‘good health’ premise of welfare, it is relevant to examine welfare more broadly and to consider the animal’s experiences.” In outlining this, the authors highlight that the animals used in this kind of research do not just suffer in particular procedures, but may also suffer throughout their lives in this disease induced state. In a later section of the paper, discussing how the 3 Rs are applied, the authors note that “reluctance by investigators to engage in ethical assessment of animal research follows from thinking that their scientific background does not qualify them.” In other words, the 3 Rs are, in many ways, contingent on the researchers / investigators being willing to engage in the evaluation of what animals need and desire to live better lives.

Overall, the authors believe that “better and more consistent application of the 3Rs is considered a major opportunity for scientific, economic, and humanitarian cross-benefit,” and that to do so, it is “essential to engage scientists in a more meaningful way with the 3Rs in practice.” For animal advocates, the paper is instructive in showing how the 3 Rs are a major force in the world of animal research, and demonstrates that any advocacy in the area of animal experimentation will need to be responsive to the 3 Rs in order to be relevant.

Original Abstract:
Ethics on animal use in science in Western society is based on utilitarianism, weighing the harms and benefits to the animals involved against those of the intended human beneficiaries. The 3Rs concept (Replacement, Reduction, Refinement) is both a robust framework for minimizing animal use and suffering (addressing the harms to animals) and a means of supporting high quality science and translation (addressing the benefits). The ambiguity of basic research performed early in the research continuum can sometimes make harm-benefit analysis more difficult since anticipated benefit is often an incremental contribution to a field of knowledge. On the other hand, benefit is much more evident in translational research aimed at developing treatments for direct application in humans or animals suffering from disease. Though benefit may be easier to define, it should certainly not be considered automatic. Issues related to model validity seriously compromise experiments and have been implicated as a major impediment in translation, especially in complex disease models where harms to animals can be intensified. Increased investment and activity in the 3Rs is delivering new research models, tools and approaches with reduced reliance on animal use, improved animal welfare, and improved scientific and predictive value.