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Gene Therapy and the Treatment of Muscular Dystrophy

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Gene Therapy and the Treatment of Muscular Dystrophy GENE THERAPY AND THE TREATMENT OF MUSCULAR DYSTROPHY by Lindsay C. Allen A SENIOR THESIS in GENERAL STUDIES Submitted to the General Studies Council in the College of Arts and Sciences at Texas Tech University in Partial fulfillment of the Requirements for the Degree of BACHELOR OF GENERAL STUDIES Approved DECEMBER 2001 w. • T3 .••/ -.- ACKNOWLEDGEMENTS A lot of hard work was put into researching and writing this thesis. 1 could not have done it on my ovm and would like to thank those who helped me through this. Dr. Michael San Francisco, the chairperson of my committee, gave me insights and leads on the research and the preparation of this work. I want to thank him for his time, which he gave plenty of, and his guidance through out the project. His patience was greatly appreciated. I would also like to thank Dr. Randy Allen for sending me in the right direction. He was of great help in starting the research and narrowing down my ideas. I thank Dr. Michael Schoenecke and Linda Gregston for in their guidance into and through this project. TABLE OF CONTENTS ACKNOWLEDGEMENTS ii CHAPTER I. INTRODUCTION 1 The Concept of Genetics 1 Molecular Genetics and Gene Manipulation 2 Microbiology 4 II. IN THE BEGINNING 7 ni. MICROBIOLOGY 12 rv. GENE THERAPY 15 V. MUSCULAR DYSTROPHY 21 VI. CONCLUSION 27 BIBILOGRAPHY 30 111 CHAPTER I INTRODUCTION The Concept of Genetics The idea of genetic improvement has been around for at least the past six thousand years; people have been breeding plants for specific characteristics for at least as long (Bryan 6). Charles Darwin (1809-1882) was one of the first to conceptualize the way that nature handles genetic manipulation. Although Danvin's ideas were not readily accepted at the time, he had indeed stumbled onto a natural process that had been taking place for millions of years (Bryan 6). An Austrian monk named Gregor Johann Mendel (1822-1884) is considered to be the father of genetics because he was the first to perform many experiments in gene function and elucidated some mechanisms of gene inheritance (Bryan 7). There have been many people that have contributed a great deal to the enormous amount of information in genetics that has been collected over the years. Many milestones have been passed, and there are many more to come. Genetics is a very broad field that has many facets. The accomplishments that scientists have made have already helped us better understand the bases of genes, gene expression, and development, and have enabled us to look into the possibilities of cures for disease and the prevention of some of the aihnents of humans, animals, and plants. Molecular Genetics and Gene Manipulation The human genome is the basis of human life, and total understanding of it is imperative for research into genetic disorders. Walter Gilbert wrote "The total human sequence is the grail of human genetics ... an incomparable tool for the investigation of every aspect of human function" (qtd. in Davies 12). Gene manipulation is the platform from which gene therapy stems (Hesterlee 4). Gene therapy does, after all, include manipulation of the genome to achieve desired results. Already, many disorders and genes coding for specific characteristics have been isolated (Davies 119-40). There are hopes that someday we will be able to eradicate genetic-based illnesses and disorders such as cancer, Alzheimer's, muscular dystrophy, and blood conditions, such as Hemophilia, although this is not likely. Of course there are many issues that are still being discussed daily on the moral implications of the power that we may someday have over our own genetic future. Many disorders are caused by flawed genes in the human genome; these disorders have, in the past, been incurable. Because the problem lies in the genetic code, until recent discoveries and advancements, there was no hope for these people. Some conditions that are genetic based are the many types of muscular dystrophy, amyotrophic lateral sclerosis (Lou Gehrig's disease), Tay-Sachs disease. Hemophilia, and many more. Our understanding of the human genome has allowed us to begin to undertake some of these problems. With the completion of the Human Genome sequencing project earlier this year, we now have a much clearer picture of which genes are important. There are current treatments for afflictions such as hemophilia, cystic fibrosis, and 2 Alzheimer's, but there is no cure as of yet. We can suppress some symptoms of such disorders with drugs, but many people yearn for a cure. Science is constantly testing new drugs as well as old ones to see if anything can help to stop the progression of the disease or at least to alleviate some of the discomfort associated with some of them ("Research Updates" 2). However, doctors are having a difficult time finding drugs that will work on at least most patients, and without harmful side effects. The problem in the long run is that nothing beats a cure, and so research is moving as quickly as possible to eradicate the problem. A subject that has been getting a lot of attention is viral infections. Viruses have wreaked havoc on the human body since the beginning. Since science has not been able to defeat them, research has been conducted on how they work. Viruses are not living beings; they are packaged DNA. Viruses have the ability to attach to living cells receptor sites and inject their own DNA into the cell for replication. The cell is taken over by the viral DNA and becomes a factory of sorts for new viral bodies. Sometimes the cells' DNA gets packaged into the viral bundles and thus gets transferred into other cells. Because of their hardiness and their ability to inject DNA, they have become primary gene transfer vectors for gene therapy (Whal 3). Scientists have been able to take harmless viruses and incorporate desired human genes into their DNA. When the virus infects the human cells it unwittingly delivers the desired genes. Some gene therapy has been used and the results are promising, but most of the experiments done are not long term (Whal 4). If gene therapy continues to advance, doctors might someday be able to cure these problems and stop them from being passed on to future generations. 3 Viruses are being used as transporters of healthy genes into human patients. This means that a virus has to be introduced into the person, and people are still skeptical about doing this (Glasner 23). Viruses have a bad reputation because of the havoc they can induce on the human body. Viruses are responsible for such ailments as the flu, the common cold, and the much more serious HIV virus, which is responsible for AIDS. Scientists are still working on perfecting the technique, but some of the public may not be as enthusiastic about embracing this kind of treatment because of the complications they can cause. Viruses seem to be one of the best means to an end and so research continues. Microbiology The field of microbiology has played a major role in the development of genetics. Microbiologists are responsible for many discoveries and have made possible many more scientific achievements. Since microbiology is the study of the area of biology too small to see, microbiologists are needed to be able to do any work on structures so small such as cells, organelles and, of course, DNA itself, that are impossible to see with the naked eye. They carry the knowledge of how the proteins in the body are made, used, and the problems associated with dysfunctional ones. Proteins are responsible for so many things in the body, and it is important to have a good understanding of their role in the life cycle (Fairbaim 15). Health professionals are the other aspect of the field. Microbiologists may discover ways of treatment and can isolate particular genes, but the doctors are the ones who will perform the operations and who oversee the actual treatment of the patients. 4 Doctors study the human body and can give insight on how it might react to different medications and treatments. The two fields must work closely to get real goals accomplished. The people that are affected by genetic disorders do not go to the scientists for answers; they go to their doctors, and the doctors must then be aware of the current work of the scientists and be able to relate information and discoveries to their patients. Gene therapy has only recently been incorporated into the options that patients have in treating their illnesses. Gene therapy is the manipulation of genes in order to correct a disorder that has been inherited or has been expressed due to a gene or genes mutation. The current gene therapy method that is in use today is Somatic gene therapy, which changes the genes in ordinary body cells, not reproductive cells (Bryan 44). In the future we may be able to do germ line therapy, which changes the genes in the human egg and sperm (Bryan 44). This form is more drastic, and the implications are not yet known. As scientists better imderstand different human afflictions, they are discovering new avenues of treatment. When they have a firm grasp of all aspects of what they are studying and trying to alter, then their minds are more open to possibilities they may not have seen otherwise. Although there are areas of genetics that have yet to be explored, the people working in these fields have certainly been doing their best to accomplish what they can. Genetics started out with farmers and ranchers breeding for certain traits.
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