While performing a routine genetic experiment, University of Toronto Ph.D. student Mary Cheng discovered a gene in lab mice that controls pain.
By deleting the so-called DREAM gene, her mice exhibited a significant reduction in response to pain-causing stimuli. Cheng found that “the most striking difference was in terms of abdominal pain.” Her results caused much excitement in both the scientific community and the general population.
After discovering a paper in the journal Nature relating DREAM to cellular calcium levels and possibly immune system function, Cheng’s supervisor, celebrated Toronto immunologist Josef Penninger, asked her to examine the gene’s function.
“Josef often feels in the pit of his stomach that something is going to be great,” said Cheng, “and he waits for that inspiration.” Working out of the Amgen Institute at the U of T-affiliated Ontario Cancer Institute/Princess Margaret Hospital, Cheng had no idea her research could lead to such an exciting result.
Her project began in March 1999. Cheng deleted the DREAM gene from mouse eggs and sperm, then used the modified gametes to generate a mouse that lacked the gene entirely. Removal of a gene in this way often reveals its function, yet after six months of observations and testing she couldn’t detect a problem in mice carrying the deletion.
Suspicious, she elicited help from a group of neuroscientists in Lethbridge, AB. These researchers performed 38 rigorous tests on the mice, and eventually discovered a reduced response to pain stimuli.
Beyond this effect, the mice were “more or less normal,” according to Cheng. “They had some slight motor and learning problems, but when you look at these animals you can’t tell the difference [between them and unaltered mice].”
The process by which Cheng deleted the gene—resulting in a so-called “knock-out” animal—was performed at the level of the eggs and the sperm, thus eliminating the gene from every cell in the animal. As such, using these techniques as to ameliorate pain in humans is not feasible.
“It would be very difficult to knock out a gene [in humans] the way we do, because we’re using a mouse model,” Cheng explained, “but some people have been thinking of disrupting the expression of the gene by using antisense.” This is a technique that masks the expression of an existing gene using non-invasive techniques.
“You don’t want to lose all ability to sense pain,” Cheng said. “Pain is good. The function of pain in the body is to tell us when something is not right. Removal of this ability would be quite dangerous.” In terms of the possible therapeutic value of her experiments, Cheng noted that “perhaps we can [someday] give drugs … to inhibit the [DREAM] protein; this way, [DREAM] is still there, but you’re inhibiting its function.”
In terms of her future plans, Cheng explains that the interests of society are somewhat different from her own.
“The populace is interested in the clinical applications of this information, while I am interested in understanding from a scientific perspective just how DREAM is acting to prevent pain. I want to find out what other molecules are normally involved in the pathway that regulates DREAM.”
