It is interesting to reflect back on the literature written between 1980 and 1987 regarding the prospects and anticipated first applications of human gene therapy. What were predicted with a fair degree of accuracy were the specific gene transfer technologies that would first be utilized in the initial human gene therapy protocols: liposomal-mediated gene transfer and gene transfer via replication-defective retroviral and adenoviral vectors. The vast majority of human gene transfer protocols to date have used these transfer technologies. However, it was not originally anticipated that naked DNA would be efficacious in certain specific tissues, such as muscle, for gene transfer and expression.

What were neither anticipated nor predicted with any degree of accuracy were the target diseases for the initial human gene therapy protocols. These were originally predicted to be primarily monogenetic diseases, some of which are listed in Table 1.1. However, although the very first pioneering human gene therapy protocol, performed on September 14, 1990, was for correction of adenosine deaminase deficiency disease – a milestone event in the continual evolution of modern medicine – this prediction has proved to be incorrect. Instead, reflecting back over the last few years, it is clear that most of the initial applications have been in the oncology area, and it is interesting to examine the evolution of human gene therapy over this period.