Michael Houghton, PhD

Canada Excellence in Research Chair in Virology, Li Ka Shing Institute of Virology, University of Alberta
Researcher of the month: 
Jun 2012

Fishing for breakthroughs in hepatitis C researc

When Michael Houghton was 17 years old and about to graduate from high school in Britain, he spent a week researching careers at his local library. The books were listed alphabetically and, when he reached the letter “P”, he read one about Louis Pasteur. The book reawakened a childhood interest in biology.

“I decided to become a microbiologist,” he says. “I thought it would be great to try to make a contribution that would better the human condition.”

Today, Michael Houghton, PhD, is an internationally recognized microbiologist with an expertise in hepatitis virology. He was first to identify and clone the viral genomes of hepatitis C and D. These breakthroughs helped him to develop blood-screening tests to detect these viruses, ensuring the safety of patients who need blood transfusions worldwide. 

In 2000, he received the much-coveted Albert Lasker Clinical Research Award for this work. He now holds the Canada Excellence in Research Chair in Virology at the Li Ka Shing Institute of Virology at the University of Alberta, where he has pursued his goal to develop new treatments and a low-cost vaccine against hepatitis C.

Finding hepatitis C

Houghton and colleagues Qui-Lim Choo and George Kuo at Chiron, a California-based biotechnology company, screened many tens of millions of molecular clone candidates (derived from pedigreed samples provided by Dan Bradley of the U.S. Centres for Disease Control) in their search for the cause of non-A, non-B hepatitis with negative results.

“I was strongly motivated,” he recalls. “There were times when the work was very discouraging, but I never thought of what else could I be doing that was more worthwhile. I was very committed.”

They found the virus by using what is now known as a proteomic approach, i.e., by identifying the structure and function of various viral proteins. They tested each molecular clone that they thought might be from the virus to confirm that it was derived from the viral genome.

After six years of failure, in 1989, they found a promising candidate and developed an assay to test it. They invited international clinicians to send them non-A, non-B sera under code. When they assayed these blood samples, the results were positive. They had found the virus.

“When we broke the code, my word, we were picking up all of their patients. It was clear that we’d got it,” he says. “When it passed all of our molecular and serological tests, after all those years of work, we really couldn’t believe it. I thought I must be dreaming. Can this really be the virus? It was a weird feeling to realize that it was.”

For about two years after the discovery, Houghton says he felt “like I was walking on air”.

“To be able to affect human health positively has always been my ambition,” he adds. “When you are able to succeed once or twice in your career, you’re very lucky.”

Detecting and treating hepatitis C

After discovering hepatitis C, the first priority was to protect the blood supply. At that time, transfused blood carried a 5% risk of infecting recipients with the virus. Houghton and his coworkers developed a diagnostic test now used worldwide to ensure safer blood transfusions.

He then set his sights on finding more effective treatments for patients with hepatitis C, which afflicts nearly 200 million people worldwide. With his knowledge of the virus, it didn’t take long to identify key enzymes that could be targeted and might play a role in new therapies.

“Now the challenge is to make a vaccine,” he says. “Prevention is better than cure, but developing a vaccine is a long haul. A vaccine needs to be stable, cheap and transportable around the globe.”

The work is controversial, because many researchers believed that it may be impossible to develop a vaccine that can neutralize the many different strains of hepatitis C worldwide. The hepatitis C virus has more genetic variations than the human immunodeficiency virus (HIV). There are at least 6 major strains of hepatitis C with hundreds of subtypes, and the virus is constantly evolving.

Hepatitis C vaccine on horizon

“Our goal is to translate research into a vaccine that will benefit humans,” says Houghton.

His search for a hepatitis C vaccine has taken longer than it took him to discover the virus. For the past 18 months, he and his research team at the University of Alberta have made incremental progress towards this goal, and that painstaking work shows signs that it may lead to another major breakthrough.

They have focused their efforts on testing a promising new version of an experimental vaccine that Houghton developed while working for pharmaceutical giant Novartis.

“The question was, did we succeed in making a vaccine that could elicit broadly cross-neutralizing antibodies in humans? The answer is yes,” he says.

He and his associate Dr. John Law analyzed the antibody response in 60 healthy recipients of the new experimental vaccine in the University of Alberta lab. Unexpectedly, the vaccinated blood samples were found to contain antibodies that could neutralize the in vitro infectivity of every major global strain of hepatitis C. It was the first time that any hepatitis C vaccine had achieved that goal in humans.

“They made virus-neutralizing antibodies to every single strain, despite the virus being highly variable and with the vaccine only being derived from a single strain,” says Houghton.

Over the next five to seven years, he and his team along with Dr. Lorne Tyrrell, Director of the Li Ka Shing Institute of Virology at the University of Alberta, plan to test an improved version of this vaccine in a group of Canadians with the highest risk of contracting hepatitis C: intravenous drug users.

It may take many more years for this work to yield a safe and effective vaccine, but Houghton is dedicated to the task. “I used to fish when I was younger,” he says. “If I know the big fish is in the lake, I’m quite prepared to sit there for years to try to land it.”