Cystic Fibrosis Gene Discovery and its International Press Coverage

Ronald Worton, former Molecular Genetics faculty

Among the U of T disease gene discoveries at SickKids, the discovery of the cystic fibrosis gene was no doubt the greatest achievement. Lap-Chee Tsui had come to SickKids as a post-doctoral fellow with Manuel Buchwald where he initiated a project to track the CF gene in families with two or more affected children. By 1985 he had established his own group and they had linked the gene to DNA markers on chromosome 7. With Batsheva Kerem leading the genetic mapping, Johanna Rommens began the arduous process of isolating segments of DNA from the chromosome and using them to “walk” along the chromosome using sequence hybridization to identify adjacent pieces of the genome. Frances Collins, then at the University of Michigan, joined the effort by having his lab conduct “chromosome jumping” to identify sites further along the chromosome. By 1989 the SickKids group had identified a DNA sequence thought to contain the putative gene, and in collaboration with U of T / SickKids biochemist Jack Riordan, they together identified an expressed gene from Jack’s sweat gland cDNA library that was found to harbor a small deletion in CF patients. The gene had the characteristics of a “transport regulator” and the “CFTR gene” was later identified as encoding a chloride channel. The result from four years of intense effort was published in three contiguous papers in one issue of Science in September 1989, and their linkage map graced the cover of the magazine. 
It was an achievement worthy of a major publicity effort, and it is that story that I thought you might enjoy reading about. Shortly after Science accepted the three manuscripts, they decided to accelerate the publication, giving the authors only a few days to get patents in order before publication. Then a press conference was quickly arranged and Johanna Rommens, as the lead author on the gene cloning paper, had to be tracked down by the RCMP while hiking in the Rocky Mountains so she could be at the announcement. Francis Collins flew in the night before the press conference. Meanwhile the Howard Hughes Medical Institute and the American CF Foundation, who funded some of the work, wanted a second press conference in Washington early enough to make that day’s newspapers and TV. So… our press conference was moved from 10 am to 9 am, and HHMI provided a helicopter to be on the roof of SickKids to take the participants to a private plane for the flight to Washington. I was the novice organizer of the press conference, and of course I let everyone know of the time change – everyone that is but John Dirks, the Dean of Medicine, who arrived at 10 am as everyone was leaving. That was not my finest hour. But the rest went well. Manuel Buchwald joined Lap-Chee, Francis, Jack and Johanna for the whirly-bird ride to Washington and I stayed behind to explain to the Canadian press why they could not have one-on-one interviews with the SickKids / U of T scientists. It was a memorable day.