A glass half full? That enthusiasm is still very visible these days-particularly in the media." Gene Therapy Techniques Advance as Potential Treatments for Cancer," reported Genetic Engineering ews on 1 March." The Birth of a Megamarket," proclaimed Fortune on 15 May, featuring Canji Inc., a gene-therapy company in an Diego." Gene Therapy May One Day Help Doctors Fix Ailing Hearts," announced Johns Hopkins Univer ity on 28 July." Gene Therapy Boosts Radiation Therapy for Cancer," said a University of Chicago pre s release on 31 July. Beginning with a wave of media attention ment 5 years ago. Earlier thi year, Varmus created two high-level panels to advise him on how IH should proceed. The fir t, chaired by Inder Verma, a geneticist at the Salk In titute, i looking into IH'procedures for approving gene-therapy clinical trials (see box on p. 1054). The second, cochaired by Arno Motulsky, a geneticist at the University of Wa hington, eattle, and Stuart Orkin, a hematologist at Harvard University, has been asked to chart a trategy for how NIH should invest in gene therapy, choose area to emphasi: e, and help shape guideline for medical practice. Both panels will issue recommendation by December. The Motulsky-Orkin panel is draWing a lot of interest-and some nervou nesfrom gene-therapy re earchers in part because Varmus deliberately set it up to take an independent look at the field. Varmus chose its member, he said, for their" stature in the cientific community" and because none is directly involved in running a gene-therapy company or clinical trial. Varmu's intramural adviser on gene therapy, virologi t el on Wivel, director of the IH Office of Recombinant 0 A Activities, says he" would not be surprised" if the panel suggests backing offfrom the heavy emphasis on clinical trials today. Instead, Wivel suggests, the panel may stress the importance of funding basic virology and immunology." This is the primary question," Wivel says:" Should you be doing more [clinical] trials before you've solved other major technical issues," such as making vectors more efficient and Ie toxic? These recent developments at IH, the cradle of gene therapy, suggest the oaring enthusiasm for clinical experimentation may be cooling. tering difficulties in transferring genes to adequate number of target cells and getting them expressed. This problem afflict all areas of gene therapy, but it ha become acute in efforts to treat cystic fibrosis (CF): Several CF protocol have been revised because ofside effects that may have been triggered by the adenovirus agent used to transfer genes, and some researchers say that adenovirus-ba ed therapy for CF must now be rethought (ee box on p. 1052). Faced with such fundamental problems, several biomedical leader, including IH Director Harold Varmus, are saying it's time for NIH to pause, examine what gene therapy has accompli hed, and determine what role IH hould be playing in the field." De pite the growing support for gene therapy," Varmus said at a publiC meeting in May, the field" remains at a very early stage ofdevelopment. While there are several reports ofconvincing gene tran fer and expres ion, there i still little or no evidence of therapeutic benefit in patients-or even in animal models." or, he added, i there a can en us about which gene delivery system will be most effective, and he aid he wasn't confident the field wa choosing the best line ofattack. Of particular concern to Varmus and some leaders in the field is the possibility that the intense commercial interest in gene therapy is prompting a stampede into clinical trials and pressure for quick re ults-before the basic cience has been worked out. Drew Pardoll, a Johns Hopkins …