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Collaboration solves the sequece of SARS

The Journal, A magazine for alumni and friends of the University of Winnipeg, Fall/Winter 2003

On Friday April 11, 2003 severe acute respiratory syndrome (SARS) had infected almost 3000 people in seventeen countries and killed over 100. In Vancouver, British Columbia, Obi Griffith (BSc Hons ’01) and four colleagues were clustered around a computer. Rows of DNA sequences—chains of G’s and C’s and T’s and A’s representing the four nucleotides that make up DNA—appeared on the screen.

Griffith and the Bioinformatics department team from British Columbia Cancer Agency’s (BCCA) Michael Smith Genome Sciences Centre  were smiling. Already, the computer program had assembled the DNA sequence fragments into three big pieces and only a handful of small ones. They were looking at most of the genome of the SARS virus.

“We had multiple Eureka moments,” says Griffith. “By Friday night, almost all the data was there. We knew we had it.”

Genomes are too big to sequence whole—they must be sequenced in small pieces. The SARS virus genome had been translated from its original RNA into DNA pieces that, when overlapped, encompassed the entire genome. Griffith’s job, with the help of computer programs, was to put those DNA pieces together in the correct order.

“Sometimes the computer gets it completely wrong and it’s just a mess,” says Griffith. “It’s like someone took a jigsaw puzzle and hammered it together. You can make it fit but it doesn’t look right. So we have to pull it apart and redo it.”

Griffith and three colleagues drank coffee, ate pizza and Tim Horton’s donuts and worked all night to assemble the SARS sequence.

“Even though we were tired we didn’t want to stop and go home,” says Griffith.

Finally, at 4 AM, April 12, BCCA posted the first complete SARS virus sequence, a new type of coronavirus, on the World Wide Web. With this data, international researchers could improve SARS diagnosis, track the origins of the virus and begin developing vaccines.

Griffith’s experience with collaborative research began as an undergraduate. His directed studies with Ric Moodie and Alberto Civetta in the Department of Biology resulted in a research paper in the journal Experimental Gerontology. He worked for two summers studying beetle pheromones with Desiréé Vanderwel in the Department of Chemistry. They are currently writing a research paper.

“Obi was a great guy to have around,” says Vanderwel. “He was very curious and he came up with neat ideas. He enriched the lab environment.”

Vanderwel received an email from Griffith after BCCA cracked the SARS genome sequence. “He’s usually a pretty calm guy. But he was excited with the results.”

Griffith’s SARS work was the culmination of a national collaboration. The SARS virus (Tor2 strain) came from a Toronto SARS patient. Then the National Microbiology Laboratory (NML) in Winnipeg purified the genome and sent it to BCCA.

Lisa Fernando (BSc Hons ’99) started working with the SARS virus on March 19 in NML’s highest containment laboratory, Biosafety Level 4. Fernando and her colleagues, including Adrienne Meyers (BSc Hons ’96), worked 16 to 20-hour days trying to match sequence fragments from the SARS virus with sequences from known viruses.

“It was a shot in the dark,” says Fernando, a research associate in the Special Pathogens Program. “We were trying everything under the sun—hemorrhagic viruses [such as Ebola], hantaviruses, smallpox…”

Brynn Watson (BSc ’01) and her group in the DNA Core Facility at NML did the DNA sequencing. Says Watson, “During the outbreak, our role was turning the data out as fast as possible.”

By March 24, electron microscopy and sequence data identified the SARS virus as a coronavirus.

SARS collaboration reached beyond Canada. Twelve labs (including BCCA) in nine countries shared leads and research findings by email and teleconferencing. By working together, researchers completed a scientific process that normally takes months in only four weeks.

Griffith says that he was fortunate to be involved in sequencing the SARS genome and he acknowledges the weeks of laboratory work that generated the sequences. “[Assembling the sequence data] is at the end of the process, it’s the very last step.”

Griffith, Fernando, Watson, and Meyers, together with 55 Canadian colleagues, published the genome sequence of the SARS coronavirus in the May 30 issue of the journal Science.