Gene Therapy: A New Generation of Molecular MedicineIn September 1990, eight-year-old Ashanthi DeSilva made medical history when she received the first licensed human gene therapy treatment. Ashanthi was born with a defective gene that normally produces an essential enzyme, adenosine deaminase (ADA). If left untreated, the inability to produce this enzyme causes the immune system to fatally malfunction. Four years after receiving the first of many treatments with transgenic cells containing functional ADA genes, Ashanthi was still doing well. Since that first treatment, the National Institutes of Health (NIH) has spent hundreds of millions of dollars to develop and evaluate new gene therapy protocols for a variety of genetic diseases (Marshall 1995). Gene therapy has had a profound impact not only in the treatment of genetic diseases, but also the way we look at human diseases as a whole. The following text describes the technical and ethical aspects of gene therapy. In the final section, a summary of the author's personal opinion is presented.1 Technical aspects Recombinant DNA (rDNA) technology has made it possible to transfer genes from one organism to another. The use of rDNA technology together with humans and other mammals is called gene therapy. Gene therapy can be classified into two categories, germinal and somatic (Sections 1.1 and 1.2, respectively). In general, gene therapy involves increasing the function of an absent or dysfunctional gene by introducing a functional gene into the individual's cells. If the transfer is successful, the result is a transgenic individual, who is now free from the effects of the dysfunctional gene as long as the new gene is expressed (Griffiths et al. 1996). Gene therapy has been successful in mammalian models, and potential applications for the treatment of human genetic diseases such as cystic fibrosis, ADA, and various types of cancer are now being aggressively pursued by researchers. Clinical trials have already begun (Section 1.4) (Kolberg 1994, Gibbs 1996 and Marshall 1995). 1.1 Germline Gene Therapy Germline gene therapy involves the introduction of genes into both the somatic cells and the germline of an individual. The result is not only that the individual recovers from the genetic disease, but also some of the individual's gametes may carry the altered trait. Germline gene therapy in mice has been successful, but so far protocols developed for use in mice have not been effective in humans.