Each day scientists gain more knowledge about the ability to read and write in the language of genes. This knowledge has already explained some of the once mysterious basic concepts of genetics. In even more fundamental ways, discoveries in genetics have led to novel strategies for treating disease. A leading strategy, gene therapy, has the future potential of curing many previously incurable diseases. Scientists predict that by the early years of next century, gene therapy will have become a highly sophisticated drug delivery system for the treatment and cure of these diseases. As it stands now, there are very few limits on the future of genetic research and gene therapy.
Today's gene therapy is most effective
for treating single gene, single organ disorders such as sickle cell anemia,
hemophilia, adenosine deaminase, and cystic fibrosis. Future efforts
hope to be able to treat multiple gene, multiple organ disorders such as
heart disease, cancer, diabetes and mental illness. The first step
toward treatment of these diseases is pinpointing the disorder causing
genes. Once identified, strategies must be used to determine their
function and suggestions made for alterations to alleviate the problems.
Smaller single gene disorders are easier to treat now because they are less complicated and there are less things that could possibly go wrong. In general, the bigger the gene, the greater the chance that something will go wrong with part of it. Conversely, there are certain circumstances where rather subtle differences in the defects of a single gene can make a profound difference in the patient's fate. Major flaws in huge gene structures such as the disease, Duchenne Muscular Dystrophy or DMD, result in presently incurable symptoms. Scientists are confident that they will have very realistic solutions to disorders such as this within the next twenty to twenty-five years.
Improvements in Delivery Techniques
With these advances in mind, actual delivery of the corrected genes is expected to become extremely effective and efficient in the future. The first gene therapy attempts used the patient's white blood cells as the target for gene insertion. Scientists hope to perfect techniques for using bone marrow cells as the target cells for gene insertion. Enhanced bone marrow cells have proved to be a much more powerful tool in terms of faster and longer lasting results when trying to correct these disorders. Another method being studied for gene delivery involves the use of viruses. Scientists plan to insert the genes into cells by linking them with a virus that has been crippled and rendered harmless. As part of the modification, such a virus, sometimes called a vector or vehicle, has been deliberately altered so that it can carry genes into cells but cannot then escape to infect other cells. After the cells to be treated have been temporarily removed from a patient's body, the virus or vector is used to carry the desired gene into them and then returned to the patient's body. The disadvantage of using viruses is that they infect and integrate only dividing cells. Other problems include cumbersome preparation, size constraints on inserted genes, difficulties in controlling or ensuring expression, and the potential for genetic damage due to random integration in the host genome.
Problems with Future Implementation
Like any new treatment, there are going to be problems with new gene therapy strategies. Although viral strategies have proved to be somewhat successful, scientists are still encountering several problems. Viral drugs can take effect only if they can slip past the multilayered defenses of the human immune system. Many of these gene carrying viruses are fought off by an onslaught of antibodies soon after they are detected in the bloodstream. These antibodies quickly bind up the viruses and can also cause side effects such as inflammation. Viral particles that make it to target cells face trying to penetrate the tough membrane shielding the cell's DNA. Finally, those viruses that are lucky enough to make it past the immune defenses and to infect cells do so in an unpredictable manner. They typically will insert the therapeutic gene at a random position in the cell's DNA. Then the new gene might interrupt an important sequence, actually harming the cell. Even in the best case, new genes often end up in dormant stretches of DNA where they do not get switched on frequently enough to make much of a difference in the patient. Future problems that need to be solved include: gaining access to relevant cell types for correction, assessing the total fraction of cells in a tissue that need to be corrected in order to achieve the level of expression required for correction, and regulating expression of the added gene once it is transferred into the appropriate target cells.
Integrating efficacious and workable gene therapy procedures into the health care system would signal a major development in medicine, comparable to past milestones, such as the introduction of aseptic techniques, antibiotics vaccines, and tissue transplantation. Although expectations have been fueled by the escalating enthusiasm of some investigators, industrial sponsors, and members of the media, it must be recognized that clinical efficacy in human patients has yet to be clearly established for any gene therapy protocol. This sobering reality highlights the challenge of bringing this complex technology to clinical practice. Typically, many years are required before new therapies are proved successful.
Long Term Future
Members of the scientific community are unanimous in recognizing the extra ordinary long-term potential, of gene therapy for managing and correcting human disease. The realization of long term goals requires proper development of its scientific underpinnings and validation of its utility to patients with carefully designed, controlled and evaluated clinical trials. There are several common cosmetic enhancements that might be envisioned in the future. The use of genes to correct baldness, the use of genes that encode for growth factors to promote muscle development and the use of genes to affect skin color or hair color or physical appearance are among the most common types of physical enhancement. Also the matter of improving intelligence comes into play. But, because improving intelligence calls for identifying and understanding thousands of relationships between genes, it is not likely that the genetic definition of intelligence will be understood anytime in the near future. Also being discussed seriously is the idea of using an inhalant spray to deliver copies of a good gene to airway tissues of cystic fibrosis patients instead of actually injecting the cells into the body. Chemists are also beginning to create valuable new treatment strategies by fabricating "anti-sense" segments of RNA, whose sequence is the exact opposite of an unwanted sequence, to combine with existing strands and thus block the action of specific genes. Treating cancerous tumors will also be greatly improved in the future. Malignancies are usually treated with surgery, radiation or chemotherapy. For cancer patients, researchers are now planning to treat the patients' disease with genetically altered white blood cells. Also scientists hope to use gene therapy to enhance reproductive cells in order to produce offspring that carry the same genetic modification in every cell of the body. Although these advances seem promising, some scientists fear that people might be stigmatized or become uninsurable because they carry certain genetic traits. Ultimately researchers are shooting for a single treatment that would correct enough cells to provide a permanent cure for the patient's disease. This would then lead to better medical management of disease-releated genes while being able to treat wider variations in the expression of the diseased gene.
When gene therapy finally hits the
commercial marketplace, it could dramatically reshape medicine and medical
markets. Gene therapy could quite possibly transform the American
health care system. The market growth for gene therapy is expected
to explode as we enter the next century. Estimates for the year 2002
have reached as high as $275 million dollars and are expected to surge
over the $3.5 billion mark as soon as 2005.
