Human Inheritable Genetic Modifications

Produced by the American Association for the Advancement of Science

Findings and Recommendations

September 2000

A majority of the project's working group members endorses the following findings, concerns, and recommendations.

Findings

· The working group concluded that IGM cannot presently be carried out safely and responsibly on humans. Current methods for somatic gene transfer are inefficient and unreliable because they involve addition of DNA to cells rather than correcting or replacing a mutated gene with a normal one. They are inappropriate for human germ line therapy because they cannot be shown to be safe and effective. A requirement for IGM, therefore, is the development of reliable gene correction or replacement techniques.

· With current gene addition technologies, iatrogenic genetic damage could occur as a result of the unintended germ line side effects of somatic cell therapy. These problems seem at least as great as the harmful genetic damage that might arise from intentional germ line transfers. Therefore, attention must also be given to the accompanying side effects of somatic cell therapies already in use or planned.

· The working group identified few scenarios where there was no alternative to IGM for couples to minimize the prospect that their offspring will have a specific genetic disorder. The further development of somatic cell gene transfer, moreover, will offer more options for treating one's offspring.

· Guided by the theologians - mainline Protestant, Catholic, and Jewish traditions - and ethicists on the working group, the group concluded that religious and ethical evaluations of IGM will depend on the nature of the technology, its impact on human nature, the level of safety and efficacy, and whether IGM is used for therapeutic or enhancement purposes. Ethical considerations related to the social effects of IGM, particularly its implications for social justice, will play a major role in shaping the attitudes of religious communities.

· To date, the private sector has played a prominent role in the funding of somatic cell genetic research, raising questions about the influence of commercial interests on the conduct of researchers and on the scope and direction of the research. Similar questions are likely to surface if IGM research and applications go forward. Concerns

· The ability of IGM to shape the genetic inheritance of future generations raises major ethical concerns. IGM might change attitudes toward the human person, the nature of human reproduction, and parent-child relationships. IGM could exacerbate prejudice against persons with disabilities. The introduction of IGM in a society with differential access to health care would pose significant justice issues and could introduce new, or magnify existing, inequalities.

· IGM for enhancement purposes is particularly problematic. Enhancement applications designed to produce improvements in human form or function could widen the gap between the "haves" and the "have nots" to an unprecedented extent. Efforts to improve the inherited genome of persons might commodify human reproduction and foster attempts to have "perfect" children by "correcting" their genomes. Some types of enhancement applications might lead to the imposition of harmful conceptions of normality. The dilemma is that IGM techniques developed for therapeutic purposes are likely to be suitable for enhancement applications as well. Thus, going forward with IGM to treat disease or disability will make it difficult to avoid use of such interventions for enhancement purposes even when this use is considered ethically unacceptable.

Recommendations

· Even in advance of a decision about whether to proceed with IGM as traditionally understood as gene transfer in reproductive cells, a public body should be assigned responsibility to monitor and oversee research and developments in IGM, more broadly conceptualized as any technique aimed at modifying the genes that a person can transmit to his or her offspring. Some interventions that fall within the scope of the working group's definition of IGM are already taking place without the oversight that we believe is necessary.

· It is important to promote extensive public education and discussion to ascertain societal attitudes about proceeding with IGM and to develop a meaningful process for making decisions about the future of this technology. These efforts should be informed by an understanding of the relevant science, involve an extended discussion of the cultural, religious, and ethical concerns associated with IGM, and be as open and inclusive as possible. International consultation on these matters should also be encouraged.

· If a societal decision is made to proceed with IGM, a comprehensive oversight mechanism should be put in place with authority to regulate IGM applications in both the public and private sectors. Such a mechanism would help to promote public safety, develop guidelines for the use of IGM, ensure adequate public participation in policy decisions regarding IGM, and address concerns about commercial influence and conflicts of interest.

· Any protocol for somatic cell transfer in which inheritable modifications are reasonably foreseeable should not proceed without assessing the short- and long-term risks and without proper public oversight.

· Before IGM can proceed, there should be a means in place for assessing the short- and long-term risks and benefits of such interventions. Society must decide how much evidence of safety, efficacy, and moral acceptance will be required before allowing human clinical trials or IGM applications.

· At this time, the investment of public funds in support of the clinical development of technologies for IGM is not warranted. However, basic research should proceed in molecular and cellular biology and in animals that is relevant to the feasibility and effects of germ line modification.

· Human trials of inheritable genetic changes should not be initiated until techniques are developed that meet agreed upon standards for safety and efficacy. In the case of the addition of foreign genetic material, the precise molecular change or the changes in the altered genome should be proven with molecular certainty, probably at the sequence level, to ascertain that no other changes have occurred. Furthermore, the functional effects of the designed alteration should be characterized over multiple generations to preclude slowly-developing genetic damage and the emergence of an iatrogenic genetic defect. In the case in which attempts at IGM involve precise correction of the mutant sequence and no addition of foreign material, human trials should not begin before it can be proven at the full genome sequence that only the intended genetic change, limited to only the intended site, has occurred. If it is shown at the full genome sequence level that the sequence of a functionally normal genome has been restored, there will likely be no need for multi-generation evaluation.

· The role of market forces in shaping the future of IGM research and applications should be carefully assessed to ensure that adequate attention is paid to public priorities and sensibilities.

· Existing conflict of interest guidelines governing research should be reviewed and, where appropriate, amended and vigorously enforced to address the increasing role of commercial interests in genetics research. The guidelines should specify when a financial interest in a commercial IGM venture is grounds for precluding an investigator's direct participation in a clinical trial supported by that company. They should require that investigators disclose any financial interests in the research during the informed consent process, and should prohibit researchers with a direct financial interest in a study's outcome from participating in that study's selection of patients, the informed consent process, or or the direction of the study.

 

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