Cystic fibrosis (CF) is a chronic, progressive genetic condition primarily affecting the lungs and digestive system. It leads to the production of thick, sticky mucus that can clog airways and obstruct organs like the pancreas. Understanding CF has been a gradual scientific process, evolving over centuries of observations and culminating in modern genetic discoveries.
Early Clinical Observations
Symptoms of cystic fibrosis were observed in folklore and early medical texts long before its formal recognition. Medieval European proverbs warned that “Woe to the child who tastes salty from a kiss on the brow, for he is cursed and soon will die,” indicating awareness of the characteristic salty skin of individuals with CF. This folklore often associated such children with being “bewitched” or “hexed,” attributing their early demise to supernatural causes.
Early medical descriptions also noted these signs. In 1595, Pieter Pauw, an anatomy professor, detailed findings like a “shiny pancreas” in autopsies of children believed to be bewitched. Another reference from 1606 by Juan Alonso de Fontecha also noted the salty taste. These historical observations, though lacking scientific understanding, provided early hints of a condition later identified as cystic fibrosis.
Dorothy Andersen’s Definitive Contributions
The formal recognition of cystic fibrosis as a distinct disease came through the work of Dr. Dorothy Hansine Andersen. A pathologist at Columbia University, Andersen conducted extensive studies in the 1930s. She examined infants who died from severe malnutrition and lung infections, conditions often misdiagnosed as celiac disease.
Andersen’s autopsies revealed abnormalities in the pancreas and lungs of these children. She observed fibrous cysts and lungs clogged with thick secretions, differentiating this pattern from celiac disease. Her paper, “Cystic Fibrosis of the Pancreas and Its Relation to Celiac Disease: A Clinical and Pathological Study,” published in 1938, formally described and named the condition based on her findings in 49 patients. This publication established cystic fibrosis as a distinct medical condition.
Pinpointing the Genetic Cause
Following Andersen’s work, the understanding of cystic fibrosis advanced with the discovery of its genetic basis. In 1989, a collaborative team of researchers, including Dr. Lap-Chee Tsui and Dr. Francis Collins, identified the gene responsible for CF. This gene was named the Cystic Fibrosis Transmembrane Conductance Regulator, or CFTR.
The identification of the CFTR gene was a significant breakthrough, marking the first time a specific gene was linked to a particular disease. This discovery revealed that CF is caused by mutations in the CFTR gene, which codes for an ion channel protein that regulates the movement of chloride and bicarbonate ions across cell membranes. The most common mutation, known as delta F508 (ΔF508), involves the deletion of a single amino acid, phenylalanine, at position 508 of the CFTR protein. This mutation accounts for approximately 70% of all CF alleles and leads to a misfolded protein that does not reach the cell surface, impairing chloride ion transport. The understanding of the CFTR gene and its numerous mutations, now over 1,000 identified, has been crucial for genetic testing and the development of targeted therapies.