Alternatives to Animal Experiments: Reduction, Refinement, and Replacement | 11 little impact upon the scientific community for almost two decades In 1978, physiologist David Smyth conducted a survey on the Three Rs for the Research Defense Society in England and wrote the book Alternatives to Animal Experiments, in which he used the term alternatives to refer to the Three Rs Thereafter, for those familiar with the concept, the Three Rs have become interchangeable with the word alternatives In some circles, however, the word alternatives is understood to signify only replacement Hence, in order to avoid possible misinterpretations, one of the Three Rs should precede the term alternative when discussing specific methods (reduction alternative, refinement alternative, or replacement alternative) Definition of the Three Rs A reduction alternative is a method that uses fewer animals to obtain the same amount of data or that allows more information to be obtained from a given number of animals The goal of reduction alternatives is to decrease the total number of animals that must be used In fact, reduction means better experimental design Much progress has been made in reducing the number of animals required for product safety testing This is partially due to the development of substantial databases as well as to the use of non-animal methods such as cell culture to prescreen for potential harmful effects Most companies try to obtain as much information about their products as possible before they test them in animals This has led to a large reduction in animal use In doing research, scientists can decrease the number of animals they use by appropriate experimental design of their experiments and by more precise use of statistics to analyze their results Researchers can also reduce the number of experimental animals by using everevolving cellular and molecular biological methods These systems are sometimes more suitable for testing hypotheses and for gaining substantial information prior to conducting an animal experiment Refinement alternatives are methods that minimize animal pain and distress, enhance animal well being, or use animals considered to be lower on the phylogenic scale An important consideration in developing refinement alternatives is being able to assess the level of pain an animal is experiencing In the absence of good objective measures of pain, it is appropriate to assume that if a procedure is painful to humans, it will also be painful to animals Refinement alternatives include the use of analgesics and /or anesthetics to alleviate any potential pain Animals can also experience distress when they are unable to adapt to changes in their environment, such as might be caused by frequent handling or by experimental procedures Refinement alternatives, such as properly-taught handling techniques that decrease distress, can significantly contribute to the welfare of laboratory animals Animal welfare may also be enhanced by enriching the environment of the animals during the times when they are not undergoing experimental procedures Such enrichment can range from placing species-appropriate objects for play and exploration in animal cages to group housing of social species Replacement alternatives are methods that not use live animals, such as in vitro systems The term in vitro literally means “in glass,” and refers to studies carried out on living material or components