Content area
Full Text
There has been considerable discussion about the merits and risks of germ-line gene modification in humans (1). Previous publications make it clear that this is a topic that readily provokes debate (2, 3). One of our aims is to review some of the scientific advances that contribute to the development of the technology necessary for germ-line gene transfer. A second aim is to identify some life-threatening diseases that could be candidates for germ-line intervention, and a third is to consider some of the complex ethical quandaries that necessarily attend decisions about deliberate alteration of the human germ line.
TYPES OF POTENTIAL HUMAN GENETIC INTERVENTION
One framework for discussing human genetic intervention distinguishes four categories of procedures according to their goals and target cells (4). Type 1 is somatic cell gene therapy; as applied to the treatment or prevention of disease, this type of intervention involves the correction or attempted correction of genetic defects in any of the cells of the body, with the exception of the germ or reproductive cells. Given the recent developments in the field of somatic cell gene therapy, it is appropriate to enlarge the definition to include the fact that genes can be introduced into cells to provide a new function. One example of such an approach involves the insertion of cytokine genes, such as interleukin-2, tumor necrosis factor, or granulocyte-macrophage colony-stimulating factor, into a patient's malignant cells to produce an immune response (the production of cytotoxic T cells that are specifically targeted to the tumor).
Type 2 genetic intervention involves the correction or prevention of genetic deficiencies through the transfer of properly functioning genes into reproductive cells. To achieve the desired results from this approach, it will probably be necessary to replace the faulty gene rather than add a gene, the usual technique in current somatic cell gene therapy. In germ-line alteration, gene addition would be unsatisfactory because it is not possible to predict the effects of a mixture of the normal gene and the mutated gene with respect to regulatory signals necessary for normal growth and development (5). Thus, reliable, predictable gene replacement is a needed advance before germ-line intervention can be seriously considered.
Type 3 and type 4 genetic interventions would involve the use of somatic cell or...