P. Klír and M. Pravenec
Table of Contents
I. Introduction
II. Basic Model Classification
III. Concept Definitions
A. Biological Model
B. Animal Model
C. Animal Model of Disease
1. Spontaneous Animal Mode! of Disease
a. Genetic Model of Disease
b. Naturally Acquired Animal Model of Disease
2. Artificially Evoked Animal Model of Disease
IV. Genetic Animal Model of Disease
V. Extrapolation of Experimental Data
References
I. Introduction
In addition to new methods and methological aspects, a dynamic development of biomedical research during the last 50 years has given rise to a new multi- and interdisciplinary fields of science. The overlapping of these fields naturally resulted in changes of scientific nomenclature.
During the last 15 years “model” and “modeling” have often appeared in biomedical research. MEDLINE/MEDLARS system data covering the period of 1972 to 1982 showed a remarkably stable frequency of papers dealing with modeling (2 to 2.5%) in medical literature. This is thought to be an evidence that medical science, even in the period when computers are increasingly utilized, remains at the level of empiricism.’ On the other hand, modeling seems to be used in biomedical research more extensively than at the low frequency given above, provided “model” and “modeling” are understood in a broader sense than a mere mathematical modeling.
II. Basic Model Classification
The terms of model and modeling are ambiguous. Philosophically, a model formulates a way, a method, and a means of cognition consisting of a reflection of reproduction of the studied phenomenon utilizing an artificially formed system. A similarity exists between the model and the original; the model substitutes for the object studied in the process of scientific cognition, and the investigation of the model enables us to obtain information on the original. The limits of modeling are those of analogy between the model and the object.
Models can be classified from various viewpoints. If a basic philosophical classification of models (material, ideal) is adopted, they can be employed in biomedical research even if it involves some specific features. Any real object, either natural or artificial, must be considered a material model, whereas any imaginary object represents an ideal model. Statistical models are most often used as the ideal ones in biomedical research.- Logically, a biological model, an animal model, or an animal disease model belong to the material models that are natural and exist in reality. In order that the concepts can be defined, their mutual relationships must be specified.
The first of the above-mentioned models was defined as the animal disease models It represents a living organism with an inborn, acquired, or induced pathological abnormality, similar in one or more aspects to the same phenomenon in man. This definition was adopted even by 1LAR News.4 National Research Council introduced a simple classification of animal models in I979:5 (I) spontaneous disease models. (2) experimentally provoked disease models, and (3) hitherto unavailable models necessary for research.
Both Wessler’s definition and the above-mentioned classification are concepts in a narrower sense aimed mostly at pathological processes. As the biomedical research comprises more aspects than only pathological ones, the animal model has a broader reach. In 1981, the Institute of Laboratory Animal Resources (ILAR) adopted a modified Wessier’s definition6 that could be considered a general definition of the animal model: “An animal model is a living organism in which normative biology or behavior can be studied, or in which the phenomenon in one or more respects resembles the same phenomenon in humans or other species of animals.11 This new definition specifies not only the animal disease model, but also, more generally, the animal model itself used to study normal (physiological) and abnormal (pathological) processes. Therefore, from the point of view of concept hierarchy, the animal model is superior to that of animal disease model. In both cases it represents a living organism (individual) characterized by a set of physical features and life functions, e.g., metabolism, capability of growing and development, reproduction, irritability (sensibility), heredity, and nourishment, that ensure the organism’s homeostasis and enable it to exist independently in its environment. However, not only living organisms (animals) are employed as models in biomedical research. Animal and plant models that use only body organs and tissues (at the cellular and subcellular level) have also been developed, as well as models employing populations or organisms. All these models can be generally called the biological models (biomodels).
III. Concept Definitions
A. Biological Model
A biological model is defined as a living system which, if studied according to fixed rules, allows reproduction and analogical derivation of the behavior and properties of the original system (i.e., of another living system studied by using a model analysis).7 The definition suggests that any living system in nature, both in vivo and in vitro, consisting of a set of constituents exhibiting mutual relationships and effects can become the model.
B. Animal Model
An animal model can be defined as a living organism which, if studied according to fixed rules, allows reproduction and analogical derivation of the behavior and properties of the original object (mostly man) studied by a model analysis. The definition includes models evolved to study normal and abnormal processes and regulating principles in living organisms. A problem is that the boundaries among different types of models defined below are not clear; sometimes the individual categories overlap. It is true especially for the boundaries among models used for the study of normal (physiological) and abnormal (pathological) processes. This is caused by vaguely defined biological standards and by the fact that concepts of illness and health are not distinct enough. Another reason is that often only a functional defect helps in understanding a normal physiological mechanism. Figure 1 shows a simplified scheme of classification of animal models that is generally valid for the animal models developed to study normal and abnormal processes, i.e., the animal disease models.
C. Animal Model of Disease
An animal disease model is represented by a living organism with an inborn, natural, or artificially acquired defect, suffering from a pathological process or having a disposition to the disease, the examination of which according to defined rules allows reproduction and analogical derivation of a pathological behavior and properties of the original object studied by the method of model analysis (i.e., etiology, pathogenesis, and therapy of a chosen nosological unit).
The concept of the animal disease model is inferior to that of the animal model and superior to those of spontaneous disease and evoked disease in animals.
1. Spontaneous Animal Model...