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Opinion 2.11 - Gene Therapy

Gene therapy involves the replacement or modification of a genetic variant to restore or enhance cellular function or to improve the reaction of non-genetic therapies.

Two types of gene therapy have been identified: (1) somatic cell therapy, in which human cells other than germ cells are genetically altered, and (2) germ line therapy, in which a replacement gene is integrated into the genome of human gametes or their precursors, resulting in expression of the new gene in the patient’s offspring and subsequent generations. The fundamental difference between germ line therapy and somatic cell therapy is that germ line therapy affects the welfare of subsequent generations and may be associated with increased risk and the potential for unpredictable and irreversible results. Because of the far-reaching implications of germ line therapy, it is appropriate to limit genetic intervention to somatic cells at this time.

The goal of both somatic cell and germ line therapy is to alleviate human suffering and disease by remedying disorders for which available therapies are not satisfactory. This goal should be pursued only within the ethical tradition of medicine, which gives primacy to the welfare of the patient whose safety and well-being must be vigorously protected. To the extent possible, experience with animal studies must be sufficient to assure the effectiveness and safety of the techniques used, and the predictability of the results.

Moreover, genetic manipulation generally should be utilized only for therapeutic purposes. Efforts to enhance "desirable" characteristics through the insertion of a modified or additional gene, or efforts to "improve" complex human traits--the eugenic development of offspring--are contrary not only to the ethical tradition of medicine, but also to the egalitarian values of our society. Because of the potential for abuse, genetic manipulation to affect non-disease traits may never be acceptable and perhaps should never be pursued. If it is ever allowed, at least three conditions would have to be met before it could be deemed ethically acceptable: (1) there would have to be a clear and meaningful benefit to the person, (2) there would have to be no trade-off with other characteristics or traits, and (3) all citizens would have to have equal access to the genetic technology, irrespective of income or other socioeconomic characteristics. These criteria should be viewed as a minimal, not an exhaustive, test of the ethical propriety of non-disease-related genetic intervention. As genetic technology and knowledge of the human genome develop further, additional guidelines may be required.

As gene therapy becomes feasible for a variety of human disorders, there are several practical factors to consider to ensure safe application of this technology in society. First, any gene therapy research should meet the Council’s guidelines on clinical investigation (Opinion 2.07, "Clinical Investigation") and investigators must adhere to the standards of medical practice and professional responsibility. The proposed procedure must be fully discussed with the patient and the written informed consent of the patient or the patient’s legal representative must be voluntary. Investigators must be thorough in their attempts to eliminate any unwanted viral agents from the viral vector containing the corrective gene. The potential for adverse effects of the viral delivery system must be disclosed to the patient. The effectiveness of gene therapy must be evaluated fully, including the determination of the natural history of the disease and follow-up examination of subsequent generations. Gene therapy should be pursued only after the availability or effectiveness of other possible therapies is found to be insufficient. These considerations should be reviewed, as appropriate, as procedures and scientific information develop. (I, V)

Issued December 1988; Updated June 1994 based on the report "Prenatal Genetic Screening," adopted December 1992 (Arch Fam Med. 1994; 2: 633-642), and updated June 1996.