Sometimes in science, you have to take the long view.
That’s what was going through Lorne Tyrrell’s mind a couple of years ago when he got a call from a British journalist working on a book about deserving scientists who had been passed over for the Nobel Prize. He wanted to know Tyrrell’s thoughts on Michael Houghton, his friend and colleague at the University of Alberta’s Li Ka Shing Institute of Virology.
The strength of a nation and its people depend on education and medical care. These are the country's roots. And like a tree, the deeper its roots, the more flourishing its branches and foliage.
Houghton had discovered the hepatitis C virus in 1989, groundbreaking work that led to a safer blood supply and, eventually, antiviral drugs to cure a disease that still afflicts millions worldwide. Tyrrell had nominated Houghton for the Nobel several times but still no prize.
Tyrrell told the writer he wasn’t quite ready to talk to him. “I was still sure Michael would get the prize.”
That patience was justified. This Thursday, Houghton will receive the Nobel Prize in Physiology or Medicine in a virtual ceremony from Sweden.
As it turns out, patience is nothing new to Tyrrell. As the founder of the Li Ka Shing Institute of Virology, he and others have spent decades building an “it” team that could take on some of the world’s most dangerous viruses—and prepare for the ones we don’t even know about yet.
Seed planted 100 years ago
Despite his more than 40 years in virology research, David Evans relishes lecturing students in the Intro to Virology class each year. He teaches what, for most, is “the forgotten history of viral epidemics,” including smallpox, the 1918 Spanish flu, yellow fever and the rampant diseases that killed an estimated 100 million people when Europeans first arrived in the lands now called the Americas.
He tells students there’s always another pandemic just around the corner.
“People like me have been predicting something like COVID-19 forever,” said Evans, professor of medical microbiology and immunology and former vice-dean of research in the Faculty of Medicine & Dentistry. “Like lightning, you can’t say where it will hit—but these viral outbreaks have changed history.”
Evans, like many other researchers at the U of A, has devoted his career to understanding the way viruses work, and to developing ways to prevent and treat them. And they’ve been at it for nearly a century.
It will be 100 years next year since the U.S.-based Rockefeller Foundation chose the U of A for a $500,000 endowment that eventually led to the Faculty of Medicine & Dentistry. In 1961, John Colter was hired as the chair of biochemistry, and virology research took off at the university.
“The polio vaccines were just starting to make their huge impact and it was understood that growing viruses in culture was going to be a powerful research tool,” Evans said. “John brought that excitement with him.”
One of the students Colter inspired was Lorne Tyrrell, who went on to discover and develop the first oral antiviral agent for hepatitis B, a disease with 400 million chronic carriers which kills one million each year. Tyrrell’s research attracted the first major contract between a Canadian university and a pharmaceutical company, when Glaxo Canada funded the work he was doing with chemist Morris Robins in 1987. Lamivudine was proved in clinical trials and, in 1994, was used to prevent infection in a liver transplant patient at the University of Alberta Hospital, a world first. Finally, in 1998, the drug received Health Canada and U.S. FDA approval.
Virology researchers, and funders, around the world were watching. In 1993, provincial, foundation and industry funders joined forces to launch the Glaxo Heritage Research Institute for virology at U of A, attracting new faculty members and opening the first high-containment research labs in Alberta. In 2007, a team of researchers led by David Evans was awarded federal and provincial funding for the pan-provincial Alberta Institute for Viral Immunology, which was eventually folded into the Li Ka Shing Institute of Virology.
‘The place to do virology in Canada’
Over the years, students and researchers flocked to the U of A, drawn by its growing reputation for virology and the funding that went with it. Those researchers, in turn, lured others working to uncover the secrets of viruses. Biology professor Linda Reha-Krantz studied mutations in viruses that kill bacteria. Microbiologist Jim Smiley’s work on herpes helped explain how viruses replicate and spread once they’ve invaded a cell. Microbiologist Michele Barry showed how virus-infected cells avoid being killed by the immune system.
Among my colleagues in virology across Canada and the U.S., they all viewed Alberta as the place to come and do virology in Canada.
For Evans, the star who inspired him was Grant McFadden, a new assistant professor at the time Evans was completing his doctorate in biochemistry at the U of A. McFadden got Evans hooked on studying viruses.
“McFadden was examining the idea that viruses encoded genes that mess around with the immune system and cause disease,” Evans said. “That’s taken as gospel nowadays and is very well studied, but at the time Grant was one of the very few people doing molecular virology and developing that field.”
Evans went off to do post-doc work at Berkeley and Boston, but later collaborated with McFadden on a paper about viral recombination, which is what happens when two viruses infect the same cell, combine and produce a new virus with traits of both of the originals. Evans has since spent much of his career continuing that work, including investigating ways to inactivate the COVID-19 virus and working on a vaccine.
Evans returned to the U of A in 2003 as chair of medical microbiology and immunology, drawn by the exciting work being done here. “Among my colleagues in virology across Canada and the U.S., they all viewed Alberta as the place to come and do virology in Canada.”
A ‘hunting licence’ for excellence
In 2010, the Li Ka Shing Institute of Virology opened.
The institute was in large part a result of Tyrrell’s research to treat hepatitis B. Lamivudine had become the most prescribed drug in China due to the prevalence of the disease there, so Tyrrell reached out to Hong Kong businessman Li Ka-shing. The philanthropist agreed to contribute $28 million to virology research in Edmonton, and the Government of Alberta more than matched the funding.
Then came the ace in the hole: federal funding for the Canada Excellence Research Chair. It was “like getting a hunting licence to hire an extraordinary virologist,” Evans said.
Michael Houghton, who was already a superstar in the field for his work identifying the hepatitis C virus, accepted the offer from the U of A. The Canadian government awarded Houghton and his laboratory $10 million over seven years, and he came to Alberta to continue his quest for a vaccine. A unique commercialization arm, the Applied Virology Institute, opened at the Li Ka Shing in 2013, headed by Houghton.
The final piece of the puzzle came when the Biosafety Level (BSL) III high-containment facility opened at the U of A in 2012. Funded by the Government of Alberta and the Canada Foundation for Innovation, it is the largest facility of its kind in Alberta and is designed for research with pathogens that cause serious or potentially lethal disease.
That meant that in early 2020, when the COVID-19 virus began to rear its ugly head, U of A scientists were ready to quickly begin the search for solutions.
“We knew we would need it all if a pandemic like this took place,” Evans said.
Evans came for the science but stayed for the people. “People want to help you,” he said. “I’ve seen places where there isn’t that culture. Instead of getting in the way of research, everyone tries to make it happen.”
It’s a point Houghton is also passionate about. He has refused past awards because his team wasn’t acknowledged, and he routinely gives credit to young researchers in his U of A lab who are working on vaccines for hepatitis C and COVID-19.
For researchers at the Li Ka Shing Institute, science is a team sport where the ball is the critical research that will make the world safer from viral attack. And they are keeping their eye on that ball, no matter how long the game takes.
Tomorrow in Folio: What does glow-in-the-dark eel protein have to do with cancer treatments? Learn more about the scientific questions, big and small, that are being asked and answered by virologists at the University of Alberta—and where the next breakthroughs can be expected.