TORONTO Twenty-five years ago this month, the medical world was turned on its ear with the isolation of the gene that causes cystic fibrosis, a devastating inherited disease that usually killed children by their late teens.

At the helm of the research was Lap-Chee Tsui, who led the team at Torontos Hospital for Sick Children that made the seminal discovery in collaboration with scientists at the University of Michigan.

The science of human genetics was still in its infancy at that time. Pinpointing the mutated CFTR gene came about through painstaking mapping of bits of DNA to locate the root of CF symptoms thick, sticky mucus that clogs the lungs and gums up the gastrointestinal tract, requiring patients to take scores of digestive enzymes a day so they could digest food.

The cystic fibrosis defect is really a very subtle defect, Tsui (pronounced Choy), 63, said Monday during an event at Sick Kids to mark the 1989 discovery. It didnt kill the patients (right away), but the problems accumulated slowly, and at the end the patients succumbed to infection.

Using the same analogy as he used in 1989 to explain CFTRs location on chromosome 7, Tsui said researchers first narrowed it down to somewhere between Halifax and Vancouver, then further pinpointed it in Toronto, and finally zeroed in to a certain street and then the actual house that represented the defective gene.

In the ensuing years, researchers have determined there is not only one mutation in the CF gene, but about 1,900 different defects that cause greater or lesser severity of symptoms in individual patients a scientific process Tsui likened to going into the house and turning on all the lights and taps to see which ones are faulty.

The celebrated geneticist, who left Toronto 12 years ago to become vice-chancellor and president of the University of Hong Kong, from which he just retired, called progress in understanding and treating CF since the gene was isolated very exciting.

Within two years of that discovery, other Sick Kids researchers had determined that a protein that keeps epithelial cells lining the lungs, airways and digestive system nice and moist was faulty, causing the buildup of mucus that clogs the lungs and disables the digestive system.

I think the expectation when the gene was first discovered was that it would be easy to fix because the disease was caused by a single gene, and if you replaced that gene through gene therapy, then you would be able to completely reverse the consequences of the disease, said senior scientist Christine Bear, who led that team.

And it may be that gene therapy will be part of that future therapy in CF, but right now we havent developed safe ways to do that.

Originally posted here:
Canadian researchers mark 25 years since CF gene found

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