In June 1989, as Collins and Tsui hovered over a fax machine in a freshman dorm room at Yale University, where they were attending a scientific conference, they received the news they were waiting for: Tsui's lab had found a small mutation in one particular DNA fragment which appeared in 70 percent of the chromosomes from CF patients but was absent from normal chromosomes.
Collins and Tsui realized at once that they had found the CF gene. But they had to keep quiet about it because, as Collins recalls, "in the next room was one of our major competitors. The dorm walls were pretty thin, so we had to talk in whispers and not yell and scream."
Their reports were published in Science on September 8, 1989, to wide acclaim. "Until now, cystic fibrosis could not be studied in animals," Daniel E. Koshland, the journal's editor, pointed out. The discovery of the gene would make this possible, "thus bringing the day of therapy and cure much closer." Having the gene at hand would also make it possible to diagnose CF in the unborn, even in families that had no affected members. In addition, it would allow couples to be tested before they started having children, to see if they were carriers of CF.
As the researchers examined their new gene, they found it was made up of 27 segments of DNA that code for parts of a protein. In the majority of patients,the error that caused CF was tiny: three of the gene's 250,000 base pairs were missing. This deletion led to the loss of just one amino acid out of the 1,480in the protein for which the gene coded instructions. Yet this slight change was enough to radically disrupt the function of patients' lungs, sweat glands, and pancreas.
Much has been learned since then about the function of the gene's protein, named CFTR (for CF transmembrane conductance regulator). It appears to work like a two-way pump, channeling vital compounds in and out of a cell. When it functions normally, the protein helps regulate the transfer of sodium across cell membranes and serves as a chloride channel. But in CF this process fails,and the chloride channel stays closed. The sodium, which does not move freely, builds up in the lungs and disables a natural antibiotic that would otherwise guard against a wide range of lung infections. Bacteria then thrive in the thick, sticky mucus.
< Previous | Top of page | Next >
In Toronto, Lap-Chee Tsui analyzes a stream of faxed reports from CF researchers around the world and coordinates the search for new mutations.
Photo: Kay Chernush