tissues and whole organ systems that can be accomplished only in living animals. Consequently, there will be a marked increase in use of and dependence on research involving animal models. Thus, we should recognize that there will not be a reduction in the total number of laboratory animals used. On the contrary, to take full advantage of the postgenome revolution in biomedical research, we will increasingly call on the use of animal models to solve problems of human illness.

Molecular Genetic Technology

Nevertheless, I also believe there will be a considerable reduction in the heterogeneity of animal models and species used. We will focus instead on those animal models with which we can most effectively exploit the power of molecular genetic technologies. We will observe a particularly dramatic increase in the use of rodents as novel animal models of human diseases. In contrast, at schools of medicine (and I explicitly exclude schools of veterinary medicine) I believe the use of most large animal species will decline substantially. Of course, there will be some important exceptions to this latter generalization. For example, new advances in xenotransplantation will require certain large animal models that will be uniquely useful because they have been genetically engineered for experimental, and possibly within 20 years clinical, use. Similarly, nonhuman primates will remain uniquely useful for certain purposes, such as studies in cognitive neuroscience.

I believe one of the more important consequences of the availability of new molecular technologies is that they will change the very nature of the use of laboratory animals. This use will result in new experimental capabilities. Increasingly, the basis of pain and distress in laboratory animals will not be a reflection of something done to them other than the alteration of their genes. Laboratory animals, predominantly mice, fish, and invertebrates, will be genetically manipulated in ways that result in development of disease or functional disorders. In that sense, they will resemble human beings who are genetically predisposed to different diseases. The animals will develop these disorders or diseases as a consequence of genetic alterations of the germ line.

PREDICTABLE CONSEQUENCES OF GENETIC BREEDING

I believe that our understanding of novel approaches to the treatment and prevention of human (and animal) diseases will be greater than we can even imagine today. As a corollary, however, I also believe that it is unrealistic to have as a foreseeable goal the elimination of pain and distress in experimental animal models that replicate or mimic human diseases. I submit that as long as we can develop animal models by genetic manipulation and gain novel insights into cures, preventions, and treatments of diseases, we should focus on the management rather than the elimination of pain and distress.



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