3R's - Replacement

Advances in technology have given scientists a number of alternatives to using animals in research. Use of tissue cultures and computer models are examples of alternatives that may, in some research studies, replace the need for animals.

Replacement is one of the triad of alternatives to animal research first recognized by William Russell and Rex Burch in their 1959 book "The Principles of Humane Experimental Technique." They believed that researchers have a duty to replace animal tests with other kinds of tests whenever possible.

An example of a common animal test that has been replaced with new technology is the so-called "rabbit test," an early form of pregnancy test. In the early 1920s, scientists discovered that a woman produces a hormone, called human chorionic gonadotropin (hCG), soon after becoming pregnant. They also found that rabbits injected with this hormone displayed distinct changes in their ovaries, and thus the "rabbit test" was born. In the early tests, the rabbits were euthanized so their ovaries could be examined; later refinements to the test enabled the rabbits' lives to be spared.

While modern pregnancy tests are still based on measuring hCG, it is now done directly, using either the woman's blood or urine. A simple biochemical test has eliminated the need for animal testing.

Russell and Burch distinguished between relative replacement - the use of animals to provide cells, tissue or organs for in vitro, or test tube studies - and absolute replacement in which animals are not needed at all. For example, studies using tissue cultures still typically require a biopsy or the euthanization of an animal to produce the tissue material. However, a single animal can provide tissuefor a number of cultures.

In some cases, lower organisms, such as invertebrates, plants and microorganisms, can substitute for research using vertebrates. In other cases, in silico testing - the use of computer models or simulations to replace physical experiments - can potentially replace some forms of animal research.

Replacement sometimes can occur simply from increased access to information. To ensure that research studies do not duplicate previous work, the CNPRC and UC Davis require that researchers proposing to do a study involving animals conduct a thorough literature search before they will approve the project.

Sometimes partial replacement is possible. For example, a combination of alternative methods can be used to pre-screen substances for toxicity. If preliminary tests show the substance is toxic, it need not be tested on an animal. Only a negative result would necessitate additional testing using animals.

However, it is extremely difficult to replace all animal research with alternative methods. To solve complex problems in medicine, researchers need access to all the tools of modern science, including the use of animal models when in vitro and in silico methods will not suffice. Since many types of biomedical research cannot be conducted on humans for ethical, moral and legal reasons, animals are irreplaceable for understanding disease processes and for testing new drugs, surgical methods and other treatments that benefit not just humans but other animals as well.