Finding Your Calling
As an undergraduate student in England, V. Wee Yong spent much of his time in British pubs. Partying led to poor marks, derailing his aspiration to enter medical school. He decided to pursue a graduate degree in science, biding time until he could raise his grades enough to reapply. He sent applications to universities around the world to enrol in a graduate program but only received one reply. The University of British Columbia (UBC) accepted him on a trial basis. At UBC, he promptly failed his first exam.
“In the early days, I was very unsettled, misguided, no direction,” Yong muses. “I certainly didn’t do well in school. My marks were abysmal.”
He didn’t know what he wanted, but he knew he didn’t want to be where he was. Then, as part of his graduate studies, he began obligatory work in the research laboratory. And something clicked.
“My results fell into place, and things began to make sense. After wandering aimlessly through my program for two years, a light bulb went off. That’s what fortified my desire to stay in research.”
At UBC, he studied neurochemistry and pharmacology as a graduate student. He then completed a postdoctoral fellowship in glial cell biology. In the brain, glial cells insulate, support, and supply nutrients and oxygen to neurons.
“This cell type is dysfunctional in multiple sclerosis (MS), and that led me to this area of research,” says Yong. “Because MS also involves dysfunction of the immune system, I began to pick up knowledge of neuroimmunology by myself.”
While contemplating what to do next, Yong met a visiting professor from McGill University. The neuroimmunologist had come to Yong’s supervisor’s lab at UBC to learn how to grow glial cells. The two men “got to talking”. Yong was interested in a second post-doctoral fellowship in immunology; the professor needed someone with expertise in glial cell biology. Yong was offered an assistant professorship at McGill University.
After seven years at McGill, he was offered a professorship at the University of Calgary (U of C)’s Departments of Clinical Neurosciences and Oncology. He made the move in 1996.
“Unintended steps, luck, interest, hard work and opportunity led me to where I am,” he says.
Today, Yong has no regrets about becoming a researcher. He is a professor at the Hotchkiss Brain Institute, where he co-directs the MS program. He heads Translational Neuroscience at the U of C and is Director of the Alberta MS Network. He holds the Canada Research Chair in Neuroimmunology. In 2014, he served as president of the International Society of Neuroimmunology. He recently won the J. Allyn Taylor International Prize in Medicine.
Champion of generic drugs for MS
While studying neuroimmunology, Yong helped to identify how a particular medication for MS worked. It inhibited matrix metalloproteinases (MMPs), a group of enzymes that immune cells use to cross the blood-brain and other cell barriers. In a bid to find an affordable, non-injected treatment for MS, he began to scour the medical literature for generic drugs that might have the same effect.
He found one: minocycline, a member of the tetracycline family of antibiotics. A widely used acne treatment, the oral drug had a 40-year track record of tolerability. (U.K. doctors had records of its effects in more than 6 million patients who’d taken it for at least 6 months.)
That led Yong and his research team to study whether minocycline would reduce MS activity in animal models. Promising results were brought to the attention of neurologist Dr. Luanne Metz, a U of C professor of medicine.
Their productive, long-term collaboration led to a phase III clinical trial that showed that minocycline could delay the onset of full-blown MS after a first attack (clinically isolated syndrome) for up to 2 years. The study, published in the New England Journal of Medicine, opened a new door to an affordable treatment for early MS.
“The advantage of generic medications is that we can quickly bring them to the attention of clinicians who treat people with MS,” he says.
But Yong’s greatest challenge wasn’t in the laboratory. It was to find funding for the long investigative process that takes medicinal products from bench to bedside.
“When one works with a generic medication, it is difficult to get the industry support that is crucial for clinical trials,” he explains. “One spends a lot of time writing grants to get enough money for further experiments and clinical trials.”
“We have a number of research interests, including lab discoveries now being applied in trials of patients with progressive MS,” says Yong.
He and his research team are looking for therapies that foster the repair of myelin, the insulating sheaths around nerve fibres that are progressively destroyed in MS. Another line of investigation focuses on neuroimmunology.
Chronic overactivation of immune cells in MS has led Yong to look at how the immune system functions in other conditions. One is traumatic spinal cord injury.
“If we learn the principles behind how the immune system, activated after a spinal cord injury, eventually shuts itself off, it might help us to understand the disease process in MS,” Yong explains.
Another condition is glioblastoma, an incurable brain tumour that can deactivate immune cells that seek to destroy it. “If we learn some tricks of how the immune system becomes deactivated, we think that will help us in our work on MS.
“There are still many lessons to be learned, and adventures to be had, in neuro-immunology.”