HUMAN GENE THERAPY 16:169–177 (February 2005) © Mary Ann Liebert, Inc. Review Emergence of a Scientific and Commercial Research and Development Infrastructure for Human Gene Therapy CHRISTINE CROFTS 1 and SHELDON KRIMSKY 2 ABSTRACT A research and clinical subfield known as “human gene therapy” has grown rapidly since 1990, when the first human trials were approved in the United States. Using quantitative data, this paper describes and analyzes the research and commercial infrastructure, including academic centers, publications, intellectual property, and biotechnology firms, that has developed around the goal of discovering clinical applications for the mod- ification and transport of DNA to somatic cells. Despite setbacks and few documented successes, the subfield of human gene therapy continues to serve as an influential clinical paradigm for the treatment of inherited and noninherited diseases. 169 INTRODUCTION S EVERAL YEARS after scientists discovered how to use en- zymes to excise and anneal segments of DNA and how to transfer the recombined segments (rDNA) into mammalian cells, clinical geneticists began exploring the applications of those techniques for somatic cell gene repair, also known as hu- man gene therapy (HGT). In this paper, gene therapy is under- stood as encompassing any procedures that alter, transfer, acti- vate, or suppress genes for diagnosis, prognosis, prevention, or treatment of diseases. In 1980, a scientist at the University of California, Los An- geles used an HGT technique involving rDNA molecules to treat two individuals in their respective countries (one from Is- rael and another from Italy) in an attempt to cure their rare blood disease, -thalassemia. Although the experimental treatments neither helped nor harmed the patients, the principal clinical in- vestigator was found to be in violation of the National Insti- tutes of Health guidelines for rDNA research. It took another decade before HGT was officially sanctioned for human sub- jects in the United States. The first successful HGT treatments reported in the scien- tific literature involved a group of children afflicted with a rare genetic condition called X-linked severe combined immunode- ficiency disease (X-SCID). As of January 2005, 17 out of 18 SCID patients treated by an ex-vivo retroviral mediated gene transfer (including 10 from France and 4 from the United King- dom) “had their immunodeficiencies corrected with clear and sustained clinical benefits” (The Lancet, 2004). According to reports in the scientific literature and in meeting disclosures, 13 of 14 children with X-SCID rapidly improved. Their immune functions reached a level that permitted them to be released from the hospital. However, 3 of the 10 children treated for X- SCID in France are believed to have contracted leukemia from the treatment, which temporarily slowed down additional trials (Check, 2004, 2005). Despite the intermittent setbacks and slow starts, over the last 20 years an academic and commercial in- frastructure developed around the clinical applications of HGT, years before the first successes were reported. The prospects of HGT, widely acclaimed by start-up companies and in the pop- ular press and affirmed in the scientific literature (McCormack and Rabbitts, 2004), precipitated the growth of many centers, companies, and associations focused solely on this particular application of biotechnology. The institutional formation around HGT is especially noteworthy considering that it started well before conclusive proof of the success of gene therapy as 1 Department of Sociology, Boston College, Chestnut Hill, MA 02467. 2 Department of Urban and Environmental Policy and Planning, Tufts University, Medford, MA 02155.