B.C.’s unlikely Nobel Prize winner
Scientist who helped crack the code of human life could easily have become a welder
The late Nobel Prize winner Michael Smith was a good but not spectacular student who narrowly missed being sent to work in the trades.
Really, nothing about his Nobel adventure followed script.
As a student of modest means from a state-run elementary school, Smith needed to perform well enough on his exams to escape a life devoted to welding or stone masonry.
He qualified for a reputable academic boarding school in his hometown of Blackpool, although his mother had to forcefully persuade him to attend with “snobs,” he recalled. Boys can be cruel, and they were.
But during those years, he fell in love with the outdoors as a Boy Scout, a love that eventually led him to settle in British Columbia, Smith wrote in his Nobel biography. He worked in Vancouver during the late 1950s, but left for the University of Wisconsin in 1960.
He made it his mission to return.
His academic career flourished after he secured a position at UBC in 1966. It was there that Smith’s groundbreaking work in molecular biology helped kick down the doors of genetic medicine.
Smith’s technique for reprogramming genes — what is called “site-directed mutagenesis” — earned him the 1993 Nobel Prize for chemistry, the first ever awarded to a resident of B.C. (Technically, he shared the prize with American biochemist Kary Mullis.) The honour came 25 years ago.
While it wasn’t exactly an accident, Smith wasn’t trying to usher in a new scientific era in which the very code of life could be rewritten.
He had no desire to create this tool for anything but his own purposes, said molecular biologist Brett Finlay. “He wanted to know how to change a particular base pair in an enzyme he was studying.”
Smith developed the technique as a way to solve his own problem and later said he could never have anticipated other advances in genetics that made his new tool so transformative.
Up to that point, changing DNA meant blasting it with radiation or chemicals to create mutations, but it was imprecise in the extreme.
“He really changed our way of thinking about DNA,” said Finlay. Today’s cutting-edge gene-editing tool CRISPR is “an extension of the work Smith did. It opened a whole frontier.”
RIDICULOUSLY POWERFUL
The academic world seemed skeptical of its value at the time. Smith wrote a paper on the technique, which was rejected by the top academic journal Cell for not being of broad interest, said Finlay. The paper was finally published in 1978 in the Journal of Biological Chemistry.
Finlay was recruited by Smith when he was putting together the UBC Biotechnology Laboratory — now known as Michael Smith Laboratories in honour of its founding director — with the “radical” notion of bringing together engineers and animal and plant scientists. Smith was exuberant about discovery — anyone’s discovery.
“He would come running down the hall with a photocopied journal article saying, ‘Look at this, isn’t it neat?’” recalled Finlay.
Monday to Friday, Smith would be up and out of the house before it was light and come home in the evening absolutely exhausted, according to his son, Tom Smith. But he also thoroughly enjoyed his leisure time.
“As kids, we were lucky enough to grow up in Vancouver, with the mountains, the ocean and the outdoors. That was something my dad was passionate about besides his work,” said Tom.
When the Nobel committee finally got around to lauding Smith’s work, Michael wasn’t the first to hear it. The committee didn’t have his phone number.
“There were several Michael Smiths in Vancouver who got the call of congratulations from the Nobel committee before he did,” recalls Tom. “There are a number of them in the phone book.”
Michael Smith told The Vancouver Sun at the time: “I was lying in bed stark-naked, listening to the radio to find out if the Blue Jays had won last night, when the news came on about the Nobel Prize.”
And that’s when everything changed.
He really changed our way of thinking about DNA ... it opened a whole frontier”
Brett Finlay
Every cell in the human body contains genetic and operating instructions for every other cell in the body and how they interact to function as a human being. Smith figured out how to edit the code. That is every bit as ridiculously powerful as it sounds.
“You really need to step back to understand the enormity of the thing he is credited with creating,” said cancer researcher Marco Marra, UBC Canada Research Chair in Genome Science. “All life is reliant on genetic code.”
Smith’s technique allows researchers to make any change they want to DNA, turning cells into living laboratories for research into genetic disease.
“It is a hugely powerful and widely used technique in genomics and biology, and it has changed the world, literally,” he said.
Smith did not flip through a Lamborghini catalogue on the way home from Sweden after receiving his medal and $500,000 in prize money.
In fact, he gave nearly all of it away for schizophrenia research, Science World, and in support of women in sciences. The Michael Smith Foundation for Health Research, founded in his honour in 2001, a year after his death, continues that legacy.
Jennifer Gardy is one of a handful of scientists who have completed the “Michael Smith trifecta,” winning a Michael Smith Foundation scholarship to complete her PhD, a Michael Smith post-doctoral fellowship, and a Michael Smith Scholar Award.
“His key legacy has been establishing infrastructure in which science can thrive here in British Columbia,” said Gardy, Canada Research Chair in Public Health Genomics.
In addition to the program he built at UBC, Smith founded the Michael Smith Genome Sciences Centre.
Smith also had a knack for identifying top talent and he used Vancouver’s unique beauty and outdoor lifestyle — not to mention his condo at Whistler — as a recruitment tool.
“He created the technological platforms we all use to do this work,” said Gardy. “But he also understood the need for talented people to populate this ecosystem.”
Smith knew as a Nobel winner, he would have influence and the opportunity to build something special, which is just what he did.
“His name was synonymous with research and discovery and doing good,” said Marra. “Everyone wanted to be associated with him.”
A meeting between Marra and Smith in his office was interrupted by an unscheduled phone call from thenprime minister Jean Chretien.
“He covered the mouthpiece and told me he should probably take the call,” he said.