Lap-Chee Tsui is a Chinese Canadian molecular geneticist. His research team is responsible for finding the gene for Cystic Fibrosis (CF). Born in China and educated in Hong Kong, Dr. Tsui undertook his doctoral studies in biological sciences in the United States. After receiving his PhD, he became interested in genetics. He immigrated to Canada, where he became a Senior Scientist at the Research Institute of the Hospital for Sick Children. As well, he held a faculty position at the University of Toronto as Professor of Molecular and Medical Genetics.

Dr. Tsui’s primary research project was in the field of identifying the gene which caused cystic fibrosis. This disease is the most common lethal inherited disease among Caucasians, affecting 1 in every 2000. It is a recessive disorder, meaning that both parents have contributed a recessive gene to their offspring. About 1 in 28 Caucasians carry one recessive gene in their own genetic make-up, but their dominant gene protects them from developing the disease.

Using the same ratios that Mendel discovered in his experiments with pea plants, CF will affect 1 in 4 of the children of carrier parents (those who have one dominant and one recessive gene). Those who inherit the disease will produce thick, sticky mucous in their lungs and pancreas. This causes interference with breathing and digestion. Moreover, the pulmonary mucous provides an optimal environment for bacterial growth, so people with CF are regularly afflicted with serious lung infections. They take antibiotics on a regular basis as well as digestive enzymes capsules. Most people with CF die in childhood or young adulthood due to lung or heart complications.

Dr. Tsui, in collaboration with Dr. Francis Collins (a University of Michigan geneticist who now directs the National Human Genome Research Institute), worked to find the genetic mutation which was responsible for this disease. The challenge was enormous. Each person has 23 chromosome pairs. Chromosome 7 alone, which turned out to be the one involved in CF, has over 150 million base pairs (DNA units). Several research teams were able to determine a marker on the chromosome which helped to narrow the search for the gene. However, the task was still monumental. According to HHMI, Tsui’s present research institute, “Up to that point, looking for the CF gene had been much like trying to find a particular house without even knowing what continent it was on. Now researchers could narrow their search to an area equivalent to a particular country.” (www.hhmi.org/GeneticTrail/stalking/cf.htm)

Tsui approached the task by increasing the number of markers to narrow the scope. Collins developed a technique, called chromosome jumping, which allows researchers to travel along the chromosome at a faster pace. Together, they were able to isolate the gene that codes for cystic fibrosis. In 1989, they discovered that a mere 3 of the 250,000 base pairs were missing in people with CF. This loss, although seemingly small, caused an aberration in the protein (CFTR) which regulates the flow of sodium and chloride through the cell membrane. In particular, the chloride affects the wateriness of mucous secretions. Without the ability to allow the flow of chloride ions across the cell membrane, the mucous produced is thick and sticky. It clogs passageways in the lungs and pancreas and provides a wonderful environment for the growth of bacteria.

Thanks to the efforts of Dr. Tsui’s research team at the Hospital for Sick Children, in collaboration with Dr. Collins, we now know the genetic roots of cystic fibrosis. This discovery will directly contribute to treatment strategies for people afflicted with CF.

Bob