Gene therapy in man. Recommendations of European Medical Research Councils.

1. The purpose of gene therapy currently under consideration is the correction of genetic defects; attempts to enhance general human characteristics should not be contemplated. Only somatic cell gene therapy, resulting in non-heritable changes to particular body tissues, should be contemplated. Germline therapy, for introduction of heritable genetic modifications, is not acceptable. Further technical improvements in the expression of transferred genes in somatic cells will be necessary before successful gene therapy can be achieved even in animal models; in the meantime trials in man are not justified. 2. The most appropriate "candidate" genetic diseases for early investigation of treatment by gene therapy are single-gene disorders for which the affected gene and its regulation have been characterised. 3. In the near future, it is likely that success in the introduction of normal genes into human cells will be achieved through the use of disabled retrovirus vectors, although other techniques may advance rapidly. Much further work is required in the development of safe species-specific and tissue-specific retrovirus vectors. The methods of gene introduction should not result in the spread of gene or vector to other tissues within the body or to people in contact with the patient. The possibility of a significant increase in the predisposition of the patient to cancer should be evaluated in considering the risks and benefits of the treatment. In addition, the expression and regulation of the gene inserted should be stable and sufficient to ensure a therapeutic effect. 4. General ethical considerations applicable to any new clinical treatment apply to human gene therapy and, in the first instance, will require assessment in individual cases. In the near future it is likely that such therapy will be clinically justified in particular patients with invariably fatal or life-threatening diseases, provided informed consent is obtained and no alternative treatment is available. 5. A national body should consider all proposals for human gene therapy and ensure the application of agreed national guidelines. Early trials should be monitored by a central body.