In considering alternatives to animal research subjects, people often think about the 3R’s (Replacement, Reduction, Refinement) as only consisting of the 1R, Replacement. But all aspects of implementing the 3Rs can have profound impact on the animal subjects. If you are unable to replace your animals with a cell line, a computer model, or some other substitute for the whole animal it may be possible to substitute some stages of the protocol with alternatives or to refine the procedures or environment. The first professional to go to is the veterinarian who will have expertise with each species and concrete suggestions about reducing pain and distress as well as species specific improvements in both husbandry and procedures. Statistical expertise at the planning stage can result in Refinements to the protocol that will increase statistical rigor. This is an increase in "ethical" power as well, since low statistical power is unethical, a waste of resources of all kinds.
The concept of "alternatives" was developed in 1959, with the publication of The Principles of Human Experimental Technique by W.M.S. Russell and R.L. Burch. They proposed the three R's of research: replacement, reduction, and refinement.
Replacement is more than substituting animals with nonanimal models. In fact, replacement can be as simple as replacing a warm-blooded animal with a cold-blooded animal. An example of this is Teleost fish used in research of diabetes mellitus. Many times companion animals are replaced with less sentient animals such as rodents. Other avenues of replacement are computer simulations, tissue cultures, and many other models.
Reduction may be accomplished by simply reducing the numbers of animals used in the research. One example is proper application of statistical information. Reduction can also involve organs and tissues taken at the animal's time of death to be used for research that does not involve whole animals.
Refinement is the best quality care that can be afforded the animal. This includes all aspects of veterinary care, efforts to minimize pain and distress via anesthesia, analgesia, aseptic technique in surgery, husbandry details, and environmental enrichment. With some species, particularly primates, it is possible to train the animals with behavior enhancement. Studies in rats have shown that increased handling resulted in decreased stress during procedures. See Refinement of Research Methods with Mice and Refinement Pub-Med article listing.In addition to the 3 R's of Russell and Burch, a fourth R has recently been introduced to the scientific community. The fourth R overlaps some of the refinement techniques. Ronald Banks, D.V.M., (1995) proposed the 4th R of research as being Responsibility. He states, "Responsibility toward research animals focuses new facility design and facility renovation toward accommodation of social interaction and behavioral interplay performing approved experimentation in a manner as distress free as possible, with analgesics or anesthetics used when necessary, of sufficient efficacy and dosage to ameliorate pain and distress." We also share a responsibility to educate the public and show them that we do care about the welfare of the animals. (Animal Welfare Information Center Newsletter: Alternatives to Animal Models in Diabetes Research)
Some scientists think that this is an either/or situation, forcing them to choose between rigorous data and a “soft” attitude toward animal subjects. In fact, the reality is that this is a classic both/and occasion. Current data show that empathetic bonds with subjects actually increase the rigor of the data.
The promotion of affection towards laboratory animals has scientific and empirical underpinning. It has been shown in rabbits that frequent, gentle handling lessens the animals' fear response during stressful situations (Anderson, Denenberg, & Zarrow, 1972; Kertsen, Meijsser, & Metz, 1989). Rabbits who receive special positive attention from personnel show a markedly increased resistance to the development of atherosclerosis compared to subjects who receive no extra attention (Nerem, Levensque, & Cornhill, 1980). Regular gentle handling has a protective effect on the experimental induction of stomach ulcers in rats (Weininger, 1954)….Rather than compromising research, these human-animal bonds should be considered the very foundation of scientifically sound research methodology. …A compassionate attitude towards laboratory animals is a safeguard that these extraneous, potentially data-influencing variables are controlled as best as possible. (Compassion for Laboratory Animals: Impairment or Refinement of Research Methodology?)
There is another reason for respecting empathetic bonds between animal subjects and workers: the veterinary technicians and other support staff are an integral part of any research study and enhancing the environment for the animals cannot be separated ultimately from the human milieu.
Hampshire is concerned about the medical and the emotional well-being of the animals under her care and also about the emotional needs of her staff. She says it is a "research risk" when people are upset at work and that it is not easy for people to work with animals that are sick or in pain. All staff members have opportunities to make suggestions for improving conditions for the well-being of the animals. Recently, for example, technicians were disturbed because mice were receiving injections of antibiotics in a rather large volume of fluid. One suggested that, if the antibiotic were injected in half the volume, the mice would experience less stress. The change was made. (People Doing Science)
The John’s Hopkins Center for Alternatives to Animal Testing maintains a large online resource Alternatives to Animal Testing on the Web (It is also called Altweb).
The Animal Welfare Information Center posts online publications as well as a database: Alternatives and Literature Searches. They note keyword advice, for example, “animal testing alternatives” is a phrase used to index citations in Agricola, Medline, Toxline and Cancerlit databases.
The National Institutes of Health hosts an online bibliography at: Alternatives to Animal Testing Bibliography (ALTBIB).
The Norwegian Reference Center for Laboratory Animal Science and Alternatives contains a database for online textbooks as well as information on alternatives.
Alternatives to Skin Irritation/Corrosion Testing in Animals contains abstracts of specific protocols.