solving the puzzle of cystic fibrosis and its treatments is a nobel prize-worthy breakthrough

the nomination deadline to recognize transformative discoveries for the nobel prize in physiology or medicine is fast approaching. these  nominations are by invitation only and are due by the end of january .

besides those for the lifesaving covid-19 vaccines, several others are prominent. this includes  the discovery of the cystic fibrosis gene and the drugs to treat the disease . the disease was  first identified in 1938 , and is no longer a cause of near-certain deaths in infants. today, canada leads the world with a 52-year median age of survival for patients with cystic fibrosis.

indeed, it was in canada that the field of cystic fibrosis research had its  breakthrough in 1989 when the gene that causes cystic fibrosis was discovered  along with the prevalent mutation that caused the disease. it was in toronto that geneticist lap-chee tsui, working with biochemist jack riordan and physician and geneticist francis collins, who then at the university of michigan, designed a strategy to discover not only the gene but also the mutation that causes cystic fibrosis.

single gene mutation

cystic fibrosis affects the fluidity of secretions from lungs, pancreas, liver, sweat glands and other organs, making them thicker and stickier. the recessive genetic defect is due to a mutation in a single gene. tsui had  discovered that a segment of chromosome 7 harboured the mutant gene in patients .

collins innovated methods  to zero in and whittle down the dna into fragments, and used genetic mapping markers to narrow down dna sequences housing the cystic fibrosis gene. using these fragments, the team fished out corresponding dna fragments extracted from sweat gland cells of patients.

sweat glands in cystic fibrosis patients are unable to reabsorb salts during perspiration. riordan used easily accessible tissue samples with sweat glands from cystic fibrosis patients and their parents to grow sweat gland cells. extracted rna was then used to make a dna copy, exactly as we do today for  pcr tests to detect the presence of the coronavirus that causes covid-19 .

the sequencing of this dna then enabled them to deduce a single gene product from the patients’ sweat gland cells. they then used a computer to translate the sequence into the protein this gene product generates. in this way,  tsui, riordan and collins deduced a single protein made up of 1,479 amino acids .

comparing sequenced proteins

the function of the protein they had uncovered was unknown at that time but there were clues that revealed its similarity to other proteins that transported substances including ions into and out of cells. today we understand  the mechanism of how the protein works as a channel that enables chloride ions to leave cells .

treatment breakthroughs

applying the discoveries

the immediate consequences of the breakthrough of tsui, riordan and collins in 1989 were not only for the cystic fibrosis community. in 1990, they proposed the human genome project based on the  proof of principal discovery of the cystic fibrosis gene they had uncovered .

collins left the university of michigan to direct the human genome project as head of the u.s. national human genome research institute of the national institutes of health (nih). this was followed in 2009 by his appointment as overall director of the nih, a post he held until december 2021. for the drug discovery effort, it is the talented researchers in biotech and academia that  discovered how to make the drugs and how they worked, with the most recent discovery in january 2022 .