Gene Therapy: A New Generation of Molecular MedicineIn September 1990, eight-year-old Ashanthi DeSilva made medical history when she received the first approved 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 leads to fatal immune system dysfunction. Four years after receiving the first of many treatments using transgenic cells containing functional ADA genes, Ashanthi was still doing well. Since this first treatment, the National Institutes of Health (NIH) has spent hundreds of millions of dollars developing and evaluating new gene therapy protocols for various genetic diseases (Marshall 1995). Gene therapy has had a profound impact not only in the treatment of genetic diseases, but also in the way we think about human disease as a whole. The following text describes the technical and ethical aspects of gene therapy. In the last section, a summary of the author's personal opinion is presented.1 Technical aspects Recombinant DNA (rDNA) technology has made possible the transfer of genes from one organism to another. The use of rDNA technology in conjunction with humans and other mammals is called gene therapy. Gene therapy can be classified into two categories, germline and somatic (sections 1.1 and 1.2, respectively). Generally speaking, gene therapy consists of increasing the functions 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, which 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 seen success 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 actively pursued by researchers. Clinical trials have already begun (Section 1.4) (Kolberg 1994, Gibbs 1996 & Marshall 1995).1.1 Germline gene therapy Germline gene therapy involves the introduction of genes into both the somatic cells and the germ line of a individual. The result is not only that the individual is cured of the genetic disease, but some of the individual's gametes may also 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..