The Evolution of Human Gene Therapy: A Journey from Excessive Hype to Excessive Diffidence to Reality

Unlike Athena, who emerged from the brow of Zeus fully armed and ready for her godly duties, advances in biomedicine are not born fully formed and mature. Virtually all of the therapies and preventive methods that we take for granted—cancer chemotherapy, immunization techniques, tissue transplantation, management of cardiovascular disease, and treatment of diabetes and many other metabolic and degenerative diseases—have required decades of development and incremental advance from initial concept and early proof of concept to truly effective and widely applicable clinical application. They are all still imperfect but are evolving rapidly, and their practitioners are learning from false starts, detours, reversals, and missteps. In most cases, scientists, the public, policymakers, and the media understand and accept what is often a discouragingly slow pace of advance in a difficult new science. In contrast and for many reasons, the field of gene therapy found itself in its early stages on a somewhat unusual path, with many segments of the community—basic and clinical scientists and their institutions, the public and its agents, disease foundations and patients’ interest groups, the media, and the biotechnology and pharmaceutical industries—too often expecting immediate success and not appreciating the inevitable need for slow, incremental evolutionary growth. There have been enough reviews of the history of gene therapy from concept to clinical application to establish the fact that it is still a very young discipline [1,2]. Its most obvious conceptual origins date back no further than the late 1960s and early 1970s [3], and its clinical applications began only in 1989–1990 [4,5]: a clinical history of a mere 15 to 16 years. In that relatively short period of