Evidence Should Trump Intuition by Preferring Inbred Strains to Outbred Stocks in Preclinical Research

Inbred strains of mice such as C57BL and BALB/c are more widely used in published work than outbred stocks of mice such as ICR and CD-1. In contrast, outbred stocks of rats such as Wistar and Sprague-Dawley are more widely used than inbred strains such as F344 and LEW. The properties of inbred and outbred mice and rats are briefly reviewed, and it is concluded that, with some exceptions, there is a strong case for using inbred strains in most controlled experiments. This is because they are usually more uniform, so that fewer animals are usually needed to detect a specified response and they are more repeatable, because they are genetically defined (i.e., the strain can be identified using genetic markers) and less liable to genetic change. Yet many scientists continue to use outbred animals. In Daniel Kahneman's book Thinking Fast and Slow he explains that we can answer questions in 2 ways: fast by intuition or slow by analytical reasoning. The former method is instantaneous, requires no thought but is not evidence based. Analytical reasoning is evidence based but requires hard work, which we all avoid. He has found that ...when faced with a difficult question, we often answer an easier one instead, usually without noticing the substitution. The target question of whether to choose outbred or inbred strains in controlled experiments is a difficult one requiring knowledge of the characteristics of these strains and the principles of experimental design. A substitute question, are humans and outbred stocks both genetically heterogeneous, is easily answered in the affirmative. It is likely that many scientists are intuitively answering the substitute question and are assuming that they have answered the target question. If so they may be using the wrong animals in their research. Nor is the fact that humans and outbred stocks are alike in being genetically heterogeneous a reason for using them. The whole concept of a model is that it is similar to the target in some respects but different in others. Rats and mice differ from humans in that we can control their genotype. This is a positive attribute that enormously increases their value in research. Funding organizations should support research in comparing the 2 types in real experiments.