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What are the potential medical benefits of animal cloning? So far I have mostly read about the social problems cloning could create if applied to humans.

Many readers have asked variants on this question. In the weeks to come, we plan to run several responses that will indicate the variety of viewpoints in the scientific community about cloning's ultimate potential to provide concrete medical benefits.

This reply comes from James Robl in the department of veterinary and animal sciences of the University of Massachusetts at Amherst:

"Cloning is typically thought of as the production of genetically identical individuals. The primary biomedical benefits of cloning stem more from the use of this technology in the genetic modification of animals rather than from making identical copies, however. The idea behind the cloning technique is that each of the cells in an individual contains the same set of genes and, under the right conditions, should be capable of directing the development of a new genetically identical copy of the original animal.

"For genetic modification of an animal, the important point is to have a cell type that can be grown easily in culture. One example of this kind of cell is the fibroblast. Fibroblasts are present in many different organs and tissues in the body and are responsible for, among other things, building up and tearing down the extracellular matrix that holds the cells in a tissue together. Fibroblasts can be prepared readily by placing a sliver of skin in a dish containing the correct culture media and waiting for them to grow out and attach to the bottom of the dish. Because fibroblasts are so simple to grow in culture, it is possible to use the large-scale but inefficient methods of inserting genes into cells and selecting the cells with the correctly inserted gene. Only about one out of a million cells will correctly incorporate a foreign gene using the most common versions of this technique. Inserting a gene into a specific site, which is important for several biomedical uses, therefore requires about 100 million to one billion cells for a single success. Therefore, one of the most important breakthroughs with current work is not cloning itself but the ability to turn a genetically modified cell into a fully developed animal.

"One biomedical application of the cloning technique is genetically modifying animals so that their cells and organs can be transplanted into humans. Normally, cells or organs from one individual (even one of the same species) will be rejected by another; the host recognizes the graft as foreign because of differences in surface molecules on the cells. The graft is then rejected by the body's defense mechanisms and destroyed, just as if it were a disease-causing organism. Genetic modification can be used to disguise an animal's cells and organs and thereby reduce or even eliminate rejection of the graft. Thousands of people die every year because of the unavailability of human organs for transplantation. Genetically modified animal organs could begin to fill this need.

"Many other diseases could be treated by the transplantation of genetically altered cells. For example, Parkinson's, Alzheimer's and Huntington's diseases are caused by the death of specific cells in the brain. Preliminary research has shown that it is possible to alleviate the symptoms of Parkinson's disease by transplanting fetal pig brain cells into a patient's brains. A related technique may be applied to diabetes, another widespread disorder. Currently diabetics rely on insulin therapy, which is far from being an ideal treatment and is certainly not a cure. The transplantation of genetically modified animal pancreatic islet cells--which could secrete insulin in response to the body's varying glucose levels, just as the cells in a healthy individual do--could effectively cure the disease. There are numerous other examples, so transplantation therapy could potentially relieve suffering in many thousands or even millions of patients.

"Another important application of cloning technology (through both the genetic modification of animals and the creation of identical copies) lies in the potential to produce therapeutic proteins. Recently, researchers have demonstrated how to make such proteins in the milk of genetically modified animals. The mammary gland is a magnificent protein-manufacturing organ, and it also provides a convenient delivery system. The great value of the mammary gland is that it can synthesize the very large quantities of complex proteins, such as antibodies, that are needed for therapeutic or diagnostic purposes. These proteins are easily isolated from milk and can be administered in pure form by injection. In the future, we may drink altered milk to ward off diseases such as gastric ulcers or to treat autoimmune diseases such as some forms of arthritis.

"The discovery of a drug for the treatment of, or vaccination against, a disease is greatly facilitated if there is an animal model (an animal that mimics the behavior or responses of the human body) for testing the effectiveness of the drug. But animals are generally not susceptible to the diseases that afflict humans. AIDS is a good example. HIV, the virus that causes AIDS, either does not infect or does not cause the same disease symptoms in laboratory animals that it does in humans. It is therefore difficult to test vaccines or therapies for their potential to alleviate the symptoms of the disease. Cloning technology may be utilized to produce useful genetically modified animal models, which would greatly facilitate the development of treatments or innoculations for many diseases. Scientists are already at work developing a genetically modified rabbit model that expresses the human receptor for the virus and is susceptible to infection.

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