Elsevier

Theriogenology

Volume 69, Issue 1, January 2008, Pages 2-9
Theriogenology

Are animal models as good as we think?

https://doi.org/10.1016/j.theriogenology.2007.09.030Get rights and content

Abstract

Models have been a tool of science at least since the 18th century and serve a variety of purposes from focusing abstract thoughts to representing scaled down version of things for study. Generally, animal models are needed when it is impractical or unethical to study the target animal. Biologists have taken modeling by analogy beyond most other disciplines, deriving the relationship between model and target through evolution. The “unity in diversity” concept suggests that homology between model and target foretells functional similarities. Animal model studies have been invaluable for elucidating general strategies, pathways, processes and guiding the development of hypotheses to test in target animals. The vast majority of animals used as models are used in biomedical preclinical trials. The predictive value of those animal studies is carefully monitored, thus providing an ideal dataset for evaluating the efficacy of animal models. On average, the extrapolated results from studies using tens of millions of animals fail to accurately predict human responses. Inadequacies in experimental designs may account for some of the failure. However, recent discoveries of unexpected variation in genome organization and regulation may reveal a heretofore unknown lack of homology between model animals and target animals that could account for a significant proportion of the weakness in predictive ability. A better understanding of the mechanisms of gene regulation may provide needed insight to improve the predictability of animal models.

Section snippets

Model definitions

A model is a pattern, plan, representation, or description designed to show the structure or workings of an object, system, or concept (http://en.wikipedia.org/wiki/Animal_model). There are all kinds of models. Abstract models include molecular models, mental models, mathematical models, computer models, and conceptual models. Representational models include scale models, engineering models, fashion models, and role models. A detailed description of models for biomedical research is presented

Why do we need models?

We need models when we cannot put our hands on the object of our study (the cosmos, a molecule, string theory, etc.). An example of a conceptual model, proposed in the 50s, envisions epigenetic regulation as a ball rolling down hill between a series of mountain ranges [3], [4]. This woodcut conceptual presentation clearly provides no insight into methylation of histones, etc. but it does serve to focus the mind. We need models when our study would benefit from simplification. We need models

The model concept

The concept of models in science has been around for a long time. The idea of reasoning by analogy can be traced back to the 18th century when Kant in 1790 in “The critique of judgment” proposed that at least in a qualitative way, similarities among things could be used to predict cause and effect relationships, even if other differences exist [1].

This concept of modeling by analogy is pervasive in most fields of scientific investigations and was established long before the concept of

What makes a good animal model?

Many of us have an innate bias in choosing our model. We choose to use animals with which we have experience, animals for which we have housing and care readily available, and animals we can afford to support. But sometimes the model is chosen by happenstance, as was the case when ferrets were chosen for influenza studies because they just happened to be around for dog distemper studies or for the wrong reasons as was the case when pigeon breast muscle was chosen as a model for muscle

Do animal models fulfill their promise?

The answer to that question is, it depends on the question being asked. There is no doubt the acquisition of scientific knowledge has been greatly facilitated by animal experimentation. The question we are asking here is more narrowly focused. Are animal models elucidating mechanisms and forecast outcomes of their target with adequate fidelity to validate this approach of scientific investigation? Or are such studies expanding our knowledge of the model animal without fully fulfilling their

Animal models in biomedical research – testing the predictability of animal models

Though we realize the readership of this paper is primarily interested in livestock animal models, we have chosen to focus on the biomedical literature. It provides unique opportunities to evaluate animal models because a significant goal of that literature is devoted to validating the efficacy of the animal models to predict target response or behavior. There is no such animal model quality control literature for livestock per se, but maybe there should be. In biomedical research, animal

Are animal models losing their relevancy?

Once the sequencing of the human genome was proclaimed complete we were led to believe that the genomic era was in the past and the post-genomic era was our future. The goal of the post-genomic era is to decipher the sequence information in order to understand how structure and function of the genome in the context of cells, tissues, individuals and populations determine phenotype in normal, stressed and in disease states. Through high resolution genome sequencing it has become possible to

Conclusions

The validity of the genetic discussion above is exemplified in dozens, and possibly hundreds of examples of genetic background differences within species influencing the outcome of studies [56], [57]. If animal models are shown time and again not to precisely predict behavior of the target species, what good are they? We believe the literature supports the notion that animal models are an excellent basic science tool but are less useful for the purpose most are used for, as a tool for

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