The ethical challenges of in utero gene therapy

In the past year, proposals to undertake in utero gene therapy have generated much discussion and debate. Concerns have been voiced that in utero gene therapy perhaps should never be undertaken. Although there are certainly reasons for caution with respect to the initiation of clinical trials of in utero gene therapy in humans, a persuasive case has not been made that such research is unethical. There are many reasons for moving forward with in utero interventions. The most important is that for some diseases and disorders it makes sense to try to intervene as early as possible so as to prevent or slow dysfunction and morbidity. In addition, the developing fetus may be a better candidate for gene therapy than the adult. Stable and widespread gene engraftment may be more feasible in a fetus, where stem cells or pleuripotent progenitor cells are more accessible to vectors. Furthermore, the problem of immunologic responses to the vector and transgene product (that is, the therapeutic protein), which has plagued early attempts at post-natal somatic gene therapy, may be avoided in the fetus if the genetic intervention occurs during the period of immunologic development. There are very real ethical concerns that must be addressed to undertake in utero gene therapy. Obviously, efforts at in utero gene therapy require thorough evaluation of safety and efficacy in animal models before contemplating clinical trials. Studies in animals have been promising, although more questions remain. As any research in utero poses risks of infection, immune reactions and the induction of preterm labour, and poses risks for two parties, mother and fetus, the rationale for and methods of undertaking such work must meet the highest scientific and medical standards.