Perhaps the ultimate application of recombinant DNA technology is gene therapy, the direct transfer of genes into humans to treat disease. Although it is still experimental, thousands of patients have received gene therapy, and many clinical trials are under way. Gene therapy is being used to treat genetic diseases, cancer, heart disease, and even some infectious diseases such as AIDS.

In spite of the growing number of clinical trials for gene therapy, significant problems remain in transferring foreign genes into human cells, getting them expressed, and limiting immune responses to the gene products and the vectors used to transfer the genes. There are also heightened concerns about the safety of gene therapy. In 1999, a patient participating in a gene-therapy trial had a fatal immune reaction after he was injected with a viral vector carrying a gene to treat his metabolic disorder. And five children who had undergone gene therapy for severe combined immunodeficiency disease developed leukemia that appeared to be directly related to the insertion of the retroviral gene vectors into cancer-causing genes. Despite these setbacks, gene-therapy research has moved on. Unequivocal results demonstrating positive benefits from gene therapy for several different diseases have now been published. Gene therapy has been used to successfully treat several children with a genetic disorder called X-linked adrenoleukodystrophy, a fatal disease of the central nervous system. As we saw in the introduction to this chapter, gene therapy was recently used to partly restore sight in four young adults who had been blinded by a genetic disorder.

Gene therapy conducted to date has targeted only somatic (nonreproductive) cells. Correcting a genetic defect in these cells (termed somatic gene therapy) may provide positive benefits to patients, but will not affect the genes of future generations. Gene therapy that alters germ-line (reproductive) cells (termed germ-line gene therapy) is technically possible, but raises a number of significant ethical issues because it has the ability to alter the gene pool of future generations.