understand. The clear advantage of only reporting procedures is that the animal care team within an institution can focus on ensuring animal well-being instead of in which category an animal should be placed for reporting purposes.

ETHICAL ISSUES

My final message addresses the relation between biomedical research and the ethics of animal use. Jerrold Tannenbaum of the University of California, Davis, said at the PRIM&R meeting this spring, “Ethical issues in science are determined by advances in science.” In other words, complex diseases and complex approaches to understanding disease often raise ethical questions pertaining to science. A recent example of this effect is the use of gene therapy to treat clinical problems. This exciting new technology, a spin-off of the human genome project, has developed rapidly. We are starting to see ways to treat some patients who could never before be treated. However, the pace of the science has exceeded the pace of the ethical considerations.

The use of animals in research has reached a similar juncture. Our biomedical research effort over the years has been too successful, and this success has created problems. People live longer in a more quickly moving society. As a result, problems related to aging, such as neurodegenerative diseases, cancer, and diabetes, occur more frequently. Concurrently, diseases of a modern, growing urban society, such as cardiovascular disease, mental health problems, chronic fatigue, and infectious diseases like AIDS, are more prevalent. Consequently, science has moved to the more difficult questions. The challenge to the research community has been to test scientific hypotheses related to the cause and treatment of these diseases with the best animal models that mimic these disease states while minimizing the animals' discomfort, distress, and pain.

Complex diseases require complex animal models. In response to this requirement, the scientific community has created disease models that could never have been developed without our rapid understanding of the genome. The explosive development of transgenic and gene knockout animals has opened up incredible new insights into previously difficult or impossible-to-study diseases. These new genetic models have been used with better pharmacological animal models, such as neurotoxin-treated animals to mimic Parkinson's and Alzheimer's diseases and surgically manipulated animals to replicate diseases like hypertension.

All of these approaches have permitted scientists to move to the next level of understanding, the cellular and molecular mechanisms of disease. In many laboratories, the use of animals has been replaced with alternative methods such as cell culture to study how signals are mediated within cells to change genetic expression or chemical interactions. An interesting dilemma is evolving. As we learn more about what happens inside a cell, it becomes more important to relate those findings to the whole animal. For example, the genome project is identifying hundreds of thousands of new genes that are responsible for the formation of



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