AJRCCM : 100-Y ear A nniversary . Progress along the Pathway of Discovery Leading to Treatment and Cure of Cystic Fibrosis

The initial pathological description of cystic fibrosis (CF) of the pancreas was reported in the 1930s (1, 2). Development of the sweat test (3) in the 1950s enabled clinical diagnosis and the potential for therapeutic intervention. Our understanding of the pathophysiology and genetic basis of CF exploded in the 1980s, with the discovery of abnormal chloride transport in the sweat duct (4) and respiratory tract (5, 6), followed by the discovery of the gene (7–9) leading to scientific knowledge about the gene product, the CF transmembrane conductance regulator (CFTR) protein, and how loss of CFTR function caused clinical disease. During the last 40 years, the Journal has published comprehensive reviews chronicling the scientific progress in CF (10–13). In a 1998 Journal article (14), we reviewed progress in CF research in the decade after the CF gene discovery. Using a “pathway of discovery leading to understanding and cure of a genetic disease” (Figure 1) as a blueprint, this centennial review will build on that foundation and describe how the CF community has continued to make remarkable progress.