1 The Origins, Evolution, and Directions of Human Gene Therapy

Abstract

Medicine is on the brink of a new era—that of molecular genetic medicine. As in the case of previous conceptual and technical revolutions, we are witnessing the early stages of a quantum change in the way in which we understand and confront human disease. Like previous revolutions associated with the development of the sciences of human anatomy, pathology, medical pathology, microbiology, and chemical pathology, the revolution of molecular genetics is opening doors to new and definitive approaches to therapy that were previously only the stuff of dreams and scientific fantasy. This approach has come to be called “gene therapy” and aspects of its inception and development have been reviewed elsewhere (Friedmann 1992Friedmann 1996Friedmann 1997; Weatherall 1995; Wilson 1995; Brenner 1996; Curiel et al. 1996; Wagner 1996; Blaese 1997; Felgner 1997). Interestingly, the birth and evolution of gene therapy have been, if not unique, certainly one of the more unusual scientific developments in modern biomedicine. It has become a dominant concept in the treatment of disease long before it has given its first compelling evidence of true clinical effectiveness. It is, nevertheless, an established, powerful, and inexorable driving force in modern medicine.

THE EARLY RATIONALE FOR GENE THERAPY
During the late 1960s and early 1970s, the explosion in biochemical, human, and molecular genetics led to the beginnings of a completely unprecedented new understanding of human biology: normal and abnormal. The surge of understanding of molecular genetic mechanisms defining the flow of genetic information, as well as the beginnings of an...