How BC researchers decoded the SARS genome

In late 2002, a mysterious new virus emerged in China’s Guangdong province. Three months later, the virus – Severe Acute Respiratory Syndrome, or SARS – was a worldwide epidemic, eventually affecting 8,000 people, killing 800, and wreaking havoc on tourism and local economies.

In late 2002, a mysterious new virus emerged in China’s Guangdong province. Three months later, the virus – Severe Acute Respiratory Syndrome, or SARS – was a worldwide epidemic, eventually affecting 8,000 people, killing 800, and wreaking havoc on tourism and local economies.

BC researchers were among the first to respond, dropping existing work to focus solely on identifying the virus and developing containment strategies. Within six days they had sequenced the SARS genome, and in less than a year, developed three vaccine candidates – successes that received worldwide recognition.

Drs. Marco Marra and Brett Finlay, who led the BC SARS charge, attribute their teams’ success to a combination of factors: existing state-of-the art equipment and infrastructure, an injection of dedicated funds, the enthusiastic participation of the brightest scientific minds in town, and the full support of the BC government and health research sector, including major contributions from MSFHR.

Sequencing SARS: A vital first step

Marra, Director of Canada’s Michael Smith Genome Sciences Centre at the BC Cancer Agency, recalls the rapid rise of SARS as a significant health concern.

“It became clear very quickly that coordination and cooperation were needed to get a handle on this mystery virus,” he says. “We needed to know its genetic make-up in order to control its spread.”

The Genome Sciences Centre started in 1998 with a $25 million commitment from the BC Cancer Foundation. It was further developed in 2001 with $5 million in funding from MSFHR to Genome BC, which made possible $5 million in matching funding from Genome Canada. Although the centre’s mandate is cancer-related, its genome mapping technology was just the thing to decode the SARS virus.

“Our staff basically dropped everything to focus on SARS,” says Marra, an MSFHR Senior Scholar. “From the National Microbiology Laboratory in Winnipeg, we obtained a small amount of viral RNA – five billionths of a gram – from a Toronto SARS patient who had died. Then we set about amplifying it.”

Marra credits Jaswinder Khattra, now an MSFHR-funded trainee, with developing enough material from the sample for DNA sequencing. And 24 hours later, thanks to the centre’s unique bioinformatics facility headed by Dr. Steven Jones and world-class sequencing equipment, Marra’s team was the first in the world to decode the virus.

“There were some sleepless nights that week,” recalls Marra, who received a 2008 British Columbia Innovation Council Frontiers in Research award for his SARS efforts and his work on cancer research and the Human Genome Project. “It was a highly collaborative effort, locally and nationally.”

From sequencing to solutions

The sequencing of the SARS genome paved the way for another first – the development of three potential vaccines within a year. Dr. Brett Finlay, a professor in the Michael Smith Laboratories and departments of biochemistry and molecular biology and microbiology and immunology at UBC, led the process – dubbed the SARS Accelerated Vaccine Initiative (SAVI) – with Dr. Robert Brunham, then-medical director of the BC Centre for Disease Control.

SAVI was funded by a $2.6 million provincial government grant through MSFHR, which provided the team with administrative, communications and financial systems support. “As important as the funding,” says Finlay, “was approval for their non-traditional approach: rather than progressing from one vaccine development stage to the next, all stages were initiated in parallel.”

Finlay, a UBC Peter Wall Distinguished Professor, praises the government and MSFHR for whole-heartedly endorsing the fast-track process.

“SARS was still a major threat,” says Finlay. “We couldn’t afford to take the usual 10 years to develop a vaccine.”

SAVI invited scientists across the country to submit proposals for various phases of vaccine development. “We had two criteria – is it good science, and will it get us to a vaccine quickly?” says Finlay. “If the answers were yes, those labs had funding the following day.”

Many British Columbian and Canadian scientists played key roles in SAVI, says Finlay: “There was no ‘one person’ – this was a strongly-motivated and highly-organized team approach.” This approach and a “leave your ego at the door” attitude enabled SAVI’s successes, including:

  • Rapid development of neutralizing antibodies (proteins that fight infection) – the first clue that a vaccine could work.
  • Growth of the virus in culture.
  • Identification of SARS’ major epitopes (markers that alert the immune system to a virus’s presence).
  • Testing two of the three prototype vaccines on animals within six months, and the third within a year.

“If the SARS threat had continued, the next step would have been testing in humans,” says Finlay.

Lessons learned

SARS spread to 26 countries before subsiding in July 2003, due to public health efforts aimed at early identification and isolation of patients. But the work undertaken by Marra and Finlay and their colleagues has had far-reaching consequences. As well as spawning a huge body of SARS-related research, it has demonstrated how research capacity – with support from government and funding agencies – can be mobilized to achieve immediate, potentially life-saving results.