Editors: Michio Okamoto, M.D., Norio Fujiki, M.D. & Darryl R.J. Macer, Ph.D.
It is expected that the progress of the present Human Genome Project which leads to the identification of the total arrangement of nucleotide sequences of human genes will contribute to the development of medical sciences. For instance, the accomplishment of this project is considered to contribute to the further clarification of the physiological as well as the pathophysiological significance of each gene. Production of clinically useful cytokines and hormones some of which are already widely used in clinical practice will be further promoted by the accomplishment of the Human Genome Project.
Gene diagnosis, which is already performed in clinical practice in the diagnosis of some congenital as well as acquired disorders will be more widely used as a result of the further clarification of the abnormalities of genes in various disorders. Accomplishment of the Human Genome Project will also lead to the identification of genes which predispose to developmental disorders occurring in adulthood such as diabetes mellitus, hypertension, atherosclerosis, Alzheimer's disease and some of cancers. The occurrence of these disorders has been considered to be related to the familial predisposition, which has a strong connection with a polymorphism of genes. Therefore, the genomic changes which are strongly related to the development of these acquired disorders will be clarified in near future, and this clarification will lead to the diagnosis of the predispositions which cause the development of these disorders. Gene diagnosis of these disorders, therefore, can be used for the prevention of these disorders.
Problems of bioethics which are raised by doing gene diagnosis have been already extensively discussed. How to keep the private information obtained by gene diagnosis and prohibition of usage of those information for other purposes such as the discrimination in insurance, employment, and marriage, are the major issues of the bioethics of gene diagnosis. These bioethical problems of gene diagnosis are much more important for gene diagnosis of the common disorders of adulthood, since the patient's population is high and serious disorders such as cancer and AIDS are included in those disorders. However, the gene diagnosis of those disorders has a positive aspect of preventing the development of those disorders by modifying the life style of susceptible people. We have to use those information for a positive purpose, while keeping the rules of bioethics of gene diagnosis.
Gene therapy has less bioethical problems since this treatment has been developed as one strategy to solve the problems of gene diagnosis by which untreatable congenital disorders are accurately diagnosed even before the appearance of clinical symptoms of the disorders. Even prognosis of disorders can be predicted by analyzing the abnormal genes. Gene therapy is also expected to give a breakthrough in the treatment of intractable disorders such as cancer and AIDS.
It seems natural, therefore, that over expectancy on the gene therapy has occurred among scientists as well as among lay people. Even at this time, various technologies for gene therapy have been developed and some of which are now clinically tested. More than 100 protocols have been approved and more than 500 patients have been treated by gene therapy in the world now. However, the techniques of gene therapy are still immature and further development of new technologies to replace the abnormal gene with normal gene is mandatory to improve the efficacy of gene therapy.
Because of this immaturity of technology, efficacy of gene therapy is not yet clearly demonstrated except for the cases of congenital deficiency of adenosine deaminase. Since the development of gene technology is rapid, it is expected that the development of the technique to replace the abnormal gene with normal gene, will be completed in the not so distant future, and this technique will be used in clinical gene therapy.
Guidelines for gene therapy had already been made in several countries, including Japan. In those guidelines, the target of gene therapy is restricted to somatic cells and handling of germ cells for gene therapy is prohibited. This prohibition has come from the concern not to inherit the genetic changes induced by gene therapy to the next generation. However, it is true that there are congenital disorders which can be cured only by the gene therapy of germ cells. Whether we should permit germ-cell gene therapy only to those congenital disorders or not is an important issue which needs further discussion.
Another issue which is raised as the bioethical problem of gene therapy is the transduction of genes into somatic cells with the purpose of enhancement. To transduce the genes into somatic cells to improve the physical power, to increase the height, to prevent baldness, and to make blue eyes is against the guidelines of gene therapy which restricts the gene transduction only for the purpose of treatment of diseases. Therefore, as long as we are keeping strictly the present system for the approval of gene therapy, the transduction of gene with the purpose of enhancement will not be materialized. However, in the future when the gene therapy has become a routine treatment and special genes effective for the purpose of enhancement have been cloned and monopolized by a company, gene therapy for enhancement may actively be done. Since the cosmetic medicine is practiced widely we have to be very careful not to introduce the gene therapy in the area of cosmetic medicine.
For the purpose of gene therapy being socially admitted, it is stressed that we have to make a tight system to prevent the misuse of gene therapy and keep it's system.