Found the gene that causes cystic fibrosis
"Knowing science can enrich your life. Basically, science is a foundation for genuine common sense."
Richard Rozmahel passes time by reading the bulletin board hanging above the wheezing printer attached to the DNA sequencer. There’s an advertisement from a company selling genetic research chemicals. They’re offering a free T-shirt sporting the words: Ultra Pure Human Being. At the bottom of the ad he reads, “Send six peel-off seals from any GIBCO BRL Enzymes and receive an I Make My Living Manipulating DNA briefcase free.”
Ain’t it the truth, thinks Rozmahel to himself as he pulls yet another variation of the same tedious experiment from the printer. He looks at the printout absently as he makes his way back to his desk in the corner of the crowded genetics lab. People and equipment take up every possible space. Shelves groan with bottles, dishes and jars. He passes a friend staring into a microscope. A big humming refrigerator juts out into the passageway. Another student wears gloves while she puts hundreds of precisely measured portions of various liquids into tiny test tubes.
Rozmahel stops suddenly, just before he gets to his desk. Something is unusual about this printout. There it is: a three-base-pair deletion — a type of genetic mutation in a sequence of DNA. DNA molecules are long chains of instructions for making proteins, which themselves are long chains of connected molecules called amino acids. Each DNA instruction comes in a three-piece unit called a three-base pair, and each one stands for a particular amino acid needed in the construction of a protein. To Rozmahel, this three-base-pair deletion is as if one bead had vanished from a precious necklace. A mutation such as this might cause something as simple as a change in eye colour or as complex as a deadly disease.
Instead of sitting down at his desk, Rozmahel rushes to show his supervisor, Dr. Tsui (pronounced “Choy”). It’s almost six o’clock and most people have left for the night, but Lap-Chee Tsui is still working.
Tsui’s office is small. When Rozmahel arrives, Tsui is hunched over the desk, poring over some other experimental results. The shelves are loaded with books. Piles of paper cover every horizontal surface. Rozmahel looks at the shabby green rug while he waits.
“What is it, Richard?” asks Tsui, with a smile.
“I’m pretty sure I’ve found a three-base-pair deletion. Look here.” He indicates the two DNA sequences, one from a healthy person’s genes and one from a person with cystic fibrosis (CF) — a fatal disease that kills about one out of every 2,000 Canadians, mostly children. Cystic fibrosis is the most common genetic disease among Caucasians. Kids who have cystic fibrosis are born with it. Half of them will die before they are 25 and few will make it past 30. It affects all the parts of the body that secrete mucus; places like the lungs, the stomach, the nose and mouth. The mucus of kids with cystic fibrosis is so thick that sometimes they cannot breathe.
Tsui looks at the printout and says, “This is very good, Richard. Now show me that it’s real.” Tsui doesn’t seem excited at all, but he knows this is a solid clue, a major hint that they have found what they are looking for: the gene for cystic fibrosis, the cause of that terrible disease. But he has had false hopes before, so he is not going to celebrate until they check this out carefully. Maybe the difference between the two gene sequences is just a normal variation between individuals. If you take any two healthy people and compare 1,000 DNA bases, you have a good chance of finding the same thing Rozmahel had just found. There are plenty of little variations between individuals.
But Tsui remembers that day — May 9, 1989 — as the day they discovered the gene for cystic fibrosis.
He and his team spent the next five months making sure that their discovery was real, doing tests over and over to see whether the results would be the same. They identified a “signature” pattern of DNA on either side of the base-pair deletion, and using that as a marker they compared 100 healthy people’s genes with the identical DNA sequence from 100 cystic fibrosis patients. By September 1989 they were sure they had the cystic fibrosis gene.
As a boy Tsui dreamed of being an architect, and he still draws all his own diagrams and slides. He did not take up genetics until after he obtained his doctorate. He was more interested in studying the nature of diseases.
After Tsui earned his bachelor’s and master’s degrees from the Chinese University of Hong Kong, he went to study at the University of Pittsburgh in the United States. Hong Kong in those days was still a British dependency and Tsui was familiar with Western ways as practised by the British, but learning to adapt to the American way of doing things was challenging. He says, “It’s like if you go to play basketball, but all your life you’ve only played soccer, it takes a while to learn not to kick the ball.”
The first job Tsui got after receiving his doctorate was in Tennessee, at Oak Ridge National Laboratory. After spending about a year there, he took a position in the Department of Genetics at the Hospital for Sick Children in Toronto, Ontario, where he worked for 20 years and made his great discoveries. In 2002 Tsui returned to Hong Kong, where he became vice-chancellor of the University of Hong Kong.