What Fish Teach Us About Hearing Loss

by Lisa Watts

Pat McKenzie

Home: Independence, Ohio

Major: Biology

I.S. Title: The Effect of Neurotrophin-3 on Noise-Induced Sensorineural Hearing Loss and the Colourless Mutant in Zebrafish

Adviser: Richard Lehtinen

Pat McKenzie knows that his I.S., which looks at the effect of a growth factor on hearing loss in zebrafish, was successful. His results even drew praise from medical school officials interviewing him this spring. But if he were to congratulate himself for anything about the project, it would be not so much for the design of his research but for the mechanics – figuring out how to nurse tiny fish embryos to life long enough to conduct his experiments.

"I had to be innovative," he says.

McKenzie has kept pet fish and fish tanks of all kinds as long as he can remember – he kept a hundred-gallon tank in Shearer House. But his zebrafish projects presented new challenges. Biologists use the half-inch long zebrafish (Brachydanio rerio) as a model for vertebrate development and genetic biology. For half of his research, McKenzie found the mutant strain of the species that he needed at a lab in Germany. The German scientists sent fragile embryos for hatching; McKenzie went through three batches over the course of his experiments.

"Scientists from UCLA called, saying they had heard I had the mutant fish. But I had to tell them that I couldn’t keep them alive," McKenzie says. "None of the faculty here have experience with fish, so I had to come up with the procedures on my own. The stock center in Germany was helpful, and a professor in England gave me a few articles. He said there’s usually an 11 percent success rate in keeping the fish alive."

For the first part of his project, McKenzie looked at noise-induced hearing loss in zebrafish. To induce noise, he borrowed a tone generator from the physics department and played a 168-decibel tone – roughly the equivalent of a plane taking off – through a speaker near the fish for twenty-four hours. The simulation of years of noise-induced damage left the fish unresponsive to noise, or deaf. Then McKenzie watched for their response as, for a few minutes each hour, he played a tone at a frequency that appeals to the fish. The control group of some sixty fish regained hearing after twelve hours. The second group of fish, which McKenzie injected with neurotropin-3 growth factor, began to respond to noise sooner, in roughly eight hours.

Pat McKenzie Secondly, McKenzie looked at hair cell regeneration in mutant zebrafish, a study which could have applications in human hair cell growth in the ear.

"We have hair cells, with cilia that protrude, in our ears. The cilia vibrate and receive sound. Zebrafish have the same cells and cilia to perceive sound. Their ears are a series of bones, with membranes that have a dark neuromass, then cilia protruding. The mutant zebrafish have no cilia sticking out, so they can’t hear."

In batches of a dozen, McKenzie would treat six mutant fish with the growth factor (which the mutants don’t possess). Scanning the fish with a spectroscope from the neighboring Ohio Agricultural Research Develop-ment Center, "I saw some cilia growth," he says. Because the fish were hard to keep alive, "the project was successful, but on a small scale."

Hailing from Independence, Ohio, McKenzie is staying close to home to attend medical school at Case Western Reserve University. Interviewers at The Cleveland Clinic, which will pay McKenzie’s Case tuition while he works in a neuroscience lab at the clinic, were impressed with his I.S. work. They want him to continue the research there, testing whether the mutant fish eventually gain some hearing. "The interviewers," McKenzie remembers, "said things like, ‘Who would have thought that this is some undergraduate’s work in Wooster, Ohio?’"

Rick Lehtinen (biology), McKenzie’s adviser, isn’t surprised. Most applicants to medical school offer top grades and standardized test scores, but few of them have really "done" science, much less designed a project the way McKenzie did.

"Obviously that’s a strength of Wooster’s I.S. program. But Pat especially worked very independently, because none of us had experience in this field. In terms of the details, he had to cover those bases himself, and he did it well."