When virologist Michael Houghton’s phone rang a little after 4 a.m. at his California home, his mind was racing. Had something bad happened? What was he about to find out? Normally, calls at such an hour do not carry good news. But, then, this call was anything but normal...
“Everything OK?” Houghton muttered when he heard his University of Alberta colleague, Lorne Tyrrell, on the other end.
“It’s wonderful,” said Tyrrell. “You just won a Nobel Prize.”
Currently, Houghton is the director of the Li Ka Shing Applied Virology Institute at the University of Alberta. He lives in Danville, California, and for the last decade, he’s been travelling between there and Edmonton to manage a portfolio of projects run by various researchers, ranging from the development of drugs for patients with Alzheimer’s to the creation of a Group A Streptococcus vaccine, and a COVID-19 vaccine.
His team is also at work on a vaccine for hepatitis C — it was that virus’s initial discovery that resulted in Houghton’s eventual Nobel Prize win. But, up until February of this year, with COVID-19 restrictions, he’d been solely working from California, connecting with colleagues remotely for several months.
There was a pause on the end of the phone line. “I think you may have it wrong,” said Houghton to Tyrrell. No one from the Nobel Foundation had actually contacted him. Besides, it had been a little over 30 years since Houghton and his colleagues had discovered a virus that had been contaminating global blood supplies for decades. Houghton, among others, thought that ship had likely sailed.
But Tyrrell believed it would happen in 2010 when he hired Houghton to come to the U of A through the Canada Excellence Research Chairs Program and he never stopped believing it. He even refused to divulge information to someone who was writing a book about those who’d been passed over for a Nobel Prize. “I said: ‘You know, it’s not over for him yet,’” says Tyrrell.
In fact, for the last few years, Tyrrell has been waking on the first Monday in October at an ungodly hour — afternoon time in Stockholm where the Nobel prize is announced — to see if his colleague’s name would appear next to the prize for physiology or medicine. On October 5, when he refreshed the screen and saw it, along with Houghton’s former colleagues Harvey J. Alter and Charles M. Rice, Tyrrell was elated.
Within a couple hours of speaking with Tyrell, the Nobel Foundation was making plans with Houghton about his speech, which would be delivered online rather than in person due to COVID-19 protocols. Meanwhile, the prize was hand delivered straight to his home by masked and gloved bodyguards from Stockholm.
It was a thrill, says Houghton, but nothing compared to the excitement of actually discovering the genetic code of the virus back in 1989. To know that his team was going to make a significant impact on the health of millions of people was a dream that had him feeling “high for two years.”
That dream dated back to Houghton’s childhood in England. At the age of 17, he started seriously considering what he wanted to do for a career. Every week, he went to the library where there was a room full of career possibilities listed in alphabetical order. He began flipping through the alphabet until he landed on M, and “microbiology” in particular. He then read about Louis Pasteur, watched a BBC series about DNA structure and developed a passion that’s sustained his career.
In 1982, he moved to Emeryville, California, to work for a start-up called Chiron Corporation, now owned by Novartis. It was there that Houghton saw a desperate need for more information about a virus that was tainting the global blood supply. Medical professionals knew it was a type of hepatitis, but nothing else. And for a long time, it was simply dubbed, non-A, non-B hepatitis.
“In the ’80s and, of course, the ’70s, if you had a blood transfusion in north America, there was a one in 20 chance you’d come out with non-A, non-B hepatitis,” says Houghton. It was especially common in patients after experiencing cardiac surgery,.
But Harvey Alter and some other colleagues had data showing that the virus could persist over many years, potentially developing into cirrhosis or liver cancer. The World Health Organization estimates today that around two to three million are infected, with 400,000 dying of the virus around the world.
Discovering the virus was not an easy task. Scientists had been searching for its genetic code for about 15 years. “Some people questioned whether anyone would ever find it,” says Tyrrell.
Rather than using the same methods that had been used to discover hepatitis A and B, Houghton’s team tried about 30 different approaches using molecular biology before one worked.
In the lab, all there was to build upon was a list of failed results. That is until about six years in when they found the clone out of about a million that they screened; it had nucleic acid that was unique to that specific virus. “It was a slow eureka moment,” says Houghton. “Over the course of a year, we had to build up evidence.” They sequenced the virus, identified it and named it hepatitis C.
His work led to the development of blood screening tests that virtually eliminated the virus in the world’s blood supplies. Infections decreased by 80 per cent and Houghton and his team identified some of the enzymes in the virus that helped with the development of anti-viral medications.
“There was a lot of pressure to succeed because if you don’t, the company could go belly up and die,” says Houghton. “But then, when you succeed, there’s another type of problem and that’s making sure that the team gets the appropriate credit.”
Houghton received many prizes and always maintained that it was a big group effort — so much so that when he was offered the prestigious Gairdner Award and the corresponding $100,000 in 2013, he turned it down because the award committee would not acknowledge key colleagues, Qui-Lim Choo and George Kuo. Tyrrell speculates if he’d accepted, he may have been offered the Nobel Prize sooner.
Houghton has no regrets when it comes to awards. But he does wish things had gone differently when it came to some professional decisions. Houghton helped develop a vaccine for SARS while at Chiron. The vaccine was successful but, since the pandemic was no longer a concern, it was never produced. Houghton says if there had been some of that vaccine stockpiled and distributed early in the COVID-19 epidemic, it may not have spread globally. “The lesson is to make sure you make the vaccine and get it ready to put on shelves just in case the next pandemic has enough sequence similarity that the vaccine would protect against it,” says Houghton.
At the beginning of February, Houghton himself was given the COVID-19 vaccine in the U.S. and he was finally able to plan a trip to the University of Alberta to catch up on some lab work. Funding had just gone through from the provincial government to help move some projects along, including a COVID-19 vaccine that had previously been stalled due to a lack of funds. The money may also go towards the hepatitis C vaccine that Houghton has been refining over many years, dating back to his time at Chiron. It’s a challenging virus to work with, but through advancements his team hopes to test the vaccine in the clinic later this year.
“Our applied virology institute is a bit like a biotech company, which is what I worked in for most of my career. You’re trying to put together a portfolio of programs that you really think could be breakthroughs in various medical areas,” says Houghton. “If you’re successful, you could end up helping a lot of patients, but you can also commercialize the product.” He’s hoping that success comes in the next few years through the work of his many colleagues — maybe in the form of some new Alzheimer’s drugs, or new cancer drugs, or antivirals for cytomegalovirus, or drugs for non-alcoholic fatty liver disease. “We just need one breakthrough to put us on the map,” Houghton says.
Technically, the university and even the province and country are already on the map now due to Houghton’s work. But that work was done long before he came to the U of A. It’s been decades since his team discovered hepatitis C; but that past breakthrough lends credibility to the research currently happening and can hopefully help secure funding. Houghton is especially hoping for change within the province where currently there are very few manufacturing facilities for the mass production of vaccines.
“We can’t just rely on oil and gas. We have to get some alternative industries,” says Houghton. “The best way to do that, I think, is through biotechnology.”
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This article appears in the May 2021 issue of Edify.