There are very few researchers in the biological sciences that would disagree with the morality of the basic tenets of the Animal Welfare Act. The problem arises when the scientists try to rectify the basic goals and philosophy of scientific investigation with what appear to be constraints on the acquisition of knowledge. When the use of live animal experimental models became too costly and time consuming by virtue of their intensive regulation, many scientists turned to cellular or organ preparations to carry on their work. While in vitro techniques provide insights into the functioning of specific biological elements, the information gained is out of context with the dynamic interactions within the total animal. Whole body physiological functioning is complex and requires a systems analysis approach for a more complete understanding. Modern technology has provided a potential resolution to this conflict of ideas.
Since the beginning of scientific exploration, mathematical models have been used to put our ideas into simple and exact expressions that have the ability to predict events in an ever-changing world. The physical sciences have had a great deal of success with the use of these quantitative models in the scientific method as a concrete technique of hypothesis formulation.
Methods are now being developed for using mathematical models of biological systems in computer simulation studies to explore hypotheses concerning basic physiology, pharmacology, and systems toxicology and to extrapolate the findings of in vitro tissue and cell culture preparations to theoretical meaning within the context of the total animal. Computerized mathematical models that simulate physiological processes can be used to theoretically test hypotheses concerning the effects of physiological and pharmacological factors on the whole animal. The model and methods then serve as a resource for those interested in exploring the possible effects of pharmacological or toxic substances and thus avoids the need for many pilot experimental studies in Iive animals.
Mathematical modeling and systems analyses have been used successfully in physiology as a means to better qualify and quantify ideas about interactions that take place among complex systems under study. These models often serve as a formal statement of hypotheses concerning proposed mechanisms of physiological functioning and when used in computer simulation studies can reveal insight into interactions among physiological variables that may not be intuitively obvious otherwise. Models used in this way can help to develop and theoretically test hypotheses concerning complex systems and can assist in development of more intelligent research protocols before they are actually performed on live animals.
One of the major stated goals of most animal welfare organizations is to refine and reduce the number of animals used in biomedical experimentation. Though computer simulation studies are not expected to totally replace responsible animal research, they can serve as a means for refining experimental protocols and thereby reducing the number of animals wasted in poorly planned studies. Intelligent research can be accomplished with the use of an algorithm such as that depicted in figure 1. In the proposed scheme there is a constant interaction between the information obtained from in vitro studies, the theoretical considerations of those findings, and the implications within the whole animal. The results of in vitro experiments are first translated into dose-response or cause-effect relations for the organ or cellular elements under study. These relations are then extrapolated to the whole animal level with the use of mathematical models. The models are then solved with the aid of computers in simulation studies to predict the dynamic results of the in vitro findings on the total system. Planned whole animal studies can then be first performed theoretically to test the integrity of the proposed protocols and to look for potential gaps in knowledge or problems in testing before live animals are utilized. The loop is complete when the results of the live protocols are fed back into the computer simulations and the models and theories are refined. Science is then advanced and the direction of future research (in vivo and in vitro) is clarified. This method also allows the scientist who does not participate in in vivo research to translate the results of his or her studies into whole animal meaning.
Thus, methods for computer simulation studies would be important in the testing and evaluation of pharmacological and toxicological agents in a number of ways that will reduce the number of animals used in basic biomedical research.
While mathematical models and computer simulations are not the perfect answer for those seeking to eliminate animals from biomedical research, they do provide some hope that our research efforts will be more thoughtful and productive. There are still a number of theoretical and philosophical issues with regard to their use in directing biological research. The many gaps in our understanding of the detailed functioning of these systems preclude the use of computer simulations in many areas. In these instances animal studies may be our only means for obtaining a complete picture. However, as our knowledge of biological systems progresses, the models will become more detailed and complex and hence can give us a greater insight into the direction of biomedical research. It is only with this continuing interaction between the experimental and the theoretical as delineated by the models can we intelligently carry out our goals in biomedical research. Not only is this the moral obligation to those who use animals in research but it is also just sound science.
Go to:
Contents, Animal Welfare Information Center Newsletter
Top of Document
The Animal Welfare Information Center
U.S. Department of Agriculture
Agricultural Research Service
National Agricultural Library
10301 Baltimore Ave.
Beltsville, MD 20705-2351
Phone: (301) 504-6212
FAX: (301) 504-7125
E-mail: awic@nal.usda.gov
