In the summer of 1990, 20-year-old Jeff Pinard set out to find the flaw in his genes that causes him to have cystic fibrosis.
He already knew quite a lot about genetic diseases, especially his own. Cystic fibrosis (CF) is a fatal disorder that clogs the lungs and other organs with a viscous, sticky mucus that interferes with breathing and digestion. It is the most common lethal inherited disease among white children and young adults, attacking about 30,000 Americans. Until recently, most patients died before reaching the age of 30. But Pinard, a microbiology major at the University of Michigan, was full of hope and could hardly contain his excitement at the thought of working with top scientists at the cutting edge of research on CF.
A year earlierin a triumph of molecular geneticsa research team headed by Francis Collins, who was then an HHMI investigator at the University of Michigan, and Lap-Chee Tsui and John Riordan of Toronto's Hospital for Sick Children had discovered an errant gene that is responsible for CF. The researchers also identified the specific mutation, a missing snippet of genetic material, involved in most cases of CF.
As many as 1 in 25 Americans of northern European descentsome 10 million peoplecarry a gene with a CF-causing defect. Babies who inherit a defective gene from both parents develop the disease.
Although Pinard had been in and out of hospitals with serious illnesses and terrible pain since he was a child, at other times he was so full of life it was difficult to remember that he constantly faced the threat of a fatal flare-up of his disease. He had been singing in choirs since he was in the sixth grade. In college, he shared an apartment near campus with another student. He often played racquetball with his friends. He rode a bicycle, and played the trumpet.
As far back as he could remember, Pinard had been interested in science. When he entered the University of Michigan as a freshman and heard about the CF research going on there, he asked if he might do volunteer work in the lab. Soon he proved so useful that the Cystic Fibrosis Foundation gave him a grant to work in the lab part-time during his sophomore year and full-time the following summer.
Pinard's presence "had a fairly profound effect on my lab," recalls Francis Collins, who is now director of the National Human Genome Research Institute. "He was all enthusiasm, good humor, smarts. Many people in the lab had had no direct contact with anyone who had the disease before. It was not so easy for them to see their work as just an intellectual exercise any more. They were much more driven by the urgency of it."
Every time Pinard coughedoften in mid-sentencehe brought a sobering reminder of the fragility of his life and that of other CF patients. At mealtimes, he had to take five pills of pancreatic enzymes so he could digest his food. He suffered from severe bacterial infections in his lungs several times a year; they were treated with antibiotics that could affect his liver. While 95 percent of CF patients die from lung complications and heart failure"the heart works so hard and has so little air coming in," Pinard explainedthe other 5 percent die of liver damage.
To keep healthy, he had to be pounded on the chest and back in eleven positions for an hour every day to shake loose the mucus that "lodges there like a thick web," he said.
Pinard's DNA was among the first to be tested by Collins' team. They found that one of his CF genes carried the Delta-F508 mutation, which they had discovered. But his other CF gene contained a then-unknown, probably milder, defect.
Hunting for his and other mutations, Pinard worked 40 to 50 hours a week in the university lab that summer. He painstakingly analyzed hundreds of DNA fragments. Before he could locate any unusual mutation, however, illness forced him back into a hospital. He had to drop out of school and go home to Grand Rapids.
But the search for new mutations goes on. Some 150 groups of scientists in over 35 different countries are now collaborating through a consortium organized by Lap-Chee Tsui in Toronto. (http://www.genet.sickkids.on.ca/cftr) They have identified more than 1000 CF mutations, most of of which affect only a very small number of patients.
The scientists understand the need for speed in getting more information about the gene, so as to develop effective treatments. As Collins puts it, "I fervently hope we'll find a cure in time to help someone like Jeff."
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