Cystic fibrosis (CF) is an inherited disorder that affects multiple organs, primarily the lungs and the digestive system, by causing the production of thick, sticky mucus. The history of understanding CF spans centuries, moving from anecdotal observations to formal clinical definition and finally to the identification of the specific genetic cause.
Early Historical Observations
The presence of CF symptoms was noted long before it received a formal medical name, most notably through European folklore. Ancient wisdom in Northern Europe contained warnings about children whose skin tasted salty when kissed. The common medieval proverb stated, “Woe to the child who tastes salty from a kiss on the brow, for he is cursed and soon will die.” The fatal nature of the condition led people to attribute the cause to witchcraft or curses, as they had no scientific explanation for the rapid decline of these infants. References dating back to the 16th century recorded autopsies of “bewitched” children that described significant damage to the pancreas, a finding that foreshadowed modern understanding.
Formal Medical Naming and Definition
The transition from folklore to formal medicine occurred in the 1930s, largely due to the work of American pathologist Dr. Dorothy Hansine Andersen. Working at Babies Hospital in New York, Dr. Andersen performed an autopsy in 1935 on a young child who had died with symptoms previously misdiagnosed as celiac disease. She discovered that the child’s lungs were severely congested, and the pancreas was riddled with fibrous cysts and lesions. Dr. Andersen reviewed records of nearly 50 similar cases that showed a consistent pattern of pancreatic damage and lung disease. In 1938, she published her paper, “Cystic fibrosis of the pancreas and its relation to celiac disease,” establishing the condition as a distinct clinical entity. She is credited with coining the initial name, which described the characteristic cystic and fibrotic changes she observed in the pancreas.
The next major clinical step came in 1953 with the discovery of the sweat electrolyte defect. Dr. Paul di Sant’Agnese observed that children with CF were experiencing severe dehydration during a New York heatwave in 1948. He noted that the children’s sweat contained abnormally high concentrations of sodium and chloride, scientifically validating the centuries-old “salty baby” folklore. This realization led to the development and standardization of the sweat test in 1959, which remains the gold standard for CF diagnosis.
Pinpointing the Genetic Cause
Although the clinical picture of CF was established, the underlying molecular cause remained unknown until the late 20th century. Researchers in the 1980s determined that the physiological defect involved poor functioning of chloride ion transport across epithelial tissues. Studies in 1983 identified that the sweat ducts of CF patients were impermeable to chloride, explaining the excessive salt loss.
The genetic breakthrough occurred in 1989 when a multi-institutional team successfully identified and cloned the gene. Key contributors included Dr. Lap-Chee Tsui and Dr. John Riordan in Toronto, and Dr. Francis Collins, then at the University of Michigan. Their work pinpointed the cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7. This gene is responsible for regulating the flow of salt and water across cell membranes in organs like the lungs, pancreas, and sweat glands. The identification of the CFTR gene and its most common mutation, Delta F508, transformed CF into a disease understood at the molecular level, opening the door for modern, targeted therapies.