To the editor–The article by Caplen et al. in your first issue" provided a welcome progress report on attempts to develop gene therapy for patients with cystic fi-brOSiS. Its cautious tone contrasted sharply with the exaggerated prospects for gene therapy claimed in the News and Views section of the same issue “. After re-counting the extraordinary progress towards gene therapy which has occurred since the discovery of the CFTR gene in 1989, and after outlining some of the major problems which remain, the author made what I believe to be unwarranted assertions. Looking into a" Crystal ball" he states that" there is no question that in vivo gene therapy for CF will be reality" finding the arguments for the continued development of in vivo gene therapy" far too compelling". He went on to conclude that" with luck and hard work it will... result in a cure for cystic fibrosis". As currently being pursued, gene therapy will not cure cystic fibrosis. Cystic fibrosis is a systemic disease affecting the pancreas, intestines, liver and reproductive system as well as the lungs. Even if the inhaled gene were to be incorporated into the genome-an outcome which is currently prohibited by international eth-ical convention-it would not reverse the damage to the pancreas or male genital tract. Nor is it likely that it would materially improve function in the lungs of thousands of patients with CF, where much damage has already occurred. We simply do not know what to expect in terms of the duration of effect of the fre-quency with which inhalations may need to be repeated, and there is considerable uncertainty about the exact respiratory epithelial cells which should be targeted. The only form of gene therapy which might be expected to" cure" cystic fibrosis with its many manifestations would be insertion of the gene during fetal life, and in this sense I agree with Dr. Crystal that gene therapy may some day be a reality. In the meantime, we should explore other promising avenues and build on the understanding of CFTR function which has been developing even more rapidly than attempts at gene therapy. For example, the observation that in cells affected by the commonest mutation, AFS08, matu-rational arrest of CFTR leads to failure of its incorporation into the apical membrane" led to the exciting discovery that