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The long, winding road to 'eureka!' Add to ...

During the 1890s, the successful British pharmacist Henry Wellcome established a pair of labs in London to conduct physiological and chemical research. Then he gave his team of researchers a mandate that most scientists today can only dream of: Follow your noses, he told them. And they did. In the face of skepticism from academics, the Wellcome labs began pumping out peer-reviewed scholarship that made an important contribution to science while putting Wellcome - a company with a promising future - on the map.

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When Willard Boyle, Canada's newest Nobel laureate, spoke disapprovingly last week about how scientists have to ante up a "business plan" in order to get funding for curiosity-driven research, his words resonated with researchers across the country. In accepting the prestigious prize - for discovering an electronic device that would lay the groundwork for the development of digital imaging - Prof. Boyle said governments are increasingly compelling scientists to focus on applied research that pays off quickly, in the form of a patent, a marketable product or a spin-off business. Cast in the language of investment portfolios, public research funders are leaning too heavily toward short-term returns at the expense of long-term growth.

Neuroscientist Bruce McNaughton has a more trenchant analogy that most politicians will recognize: "Curiosity-driven research is a bit like passenger railroads," says the renowned University of Lethbridge researcher, who recently returned to Canada after a long stint in the United States. "If you let the knowledge base, skills and infrastructure deteriorate, they are not going to be there when you need them, like we desperately do today in Canada."

It's not a new accusation. Twenty-three years ago, University of Toronto chemist John Polanyi lobbed out a similar criticism when he went to Stockholm to accept his own Nobel Prize. At the time, Brian Mulroney's Tory government was slashing funding for research while touting a "matching" grant program intended to accelerate the commercialization of university research.

Musing that ambitious young researchers would be well advised to go abroad, Prof. Polanyi warned that scientists become risk-averse if there are too many strings attached. "If they were asked three years later, 'Did you actually make some progress toward the sort of technology which you said might flow from your work?' and you would admit you didn't - because you usually don't - the sponsor of the research … simply takes the research money to someone else and asks the same impossible requirement."

Nobel winners, of course, receive a big soapbox along with their prize money and the medal. But are these lions of science simply expressing the self-importance of academe? Or have they put their fingers on a chronic source of short-sightedness embedded in Canada's overall philosophy about research and development?

About 15 years after the Wellcome labs were established, a pair of scientists working there - George Barger and James Ewens - synthesized a chemical called dopamine, a compound that one of their colleagues, Henry Dale, found to behave like the hormone adrenaline. At the time, it was little more than an interesting observation. And so the story about the recognition of dopamine's potential - which would eventually lead to dramatic advances in the treatment of neurological disorders like Parkinson's disease - ground to a halt.

On a per-capita basis, Canada doesn't do a lot of research compared with innovation-driven nations such as Finland. But since Prof. Polanyi won his Nobel in 1986, successive governments have rolled out a series of lucrative research programs dominated by conditions and specific policy goals: reversing the brain drain, improving living standards, accelerating technology transfer.

These days, the Harper government pumps hundreds of millions into energy-industry technologies such as carbon capture and storage. Yet the Tories last winter picked a fight with the scientific community by tabling a stimulus budget that proposed cutting $150-million in funding to Canada's three national research funding agencies.

To be fair, however, the pressure to commercialize science isn't just a Canadian phenomenon, notes mathematical physicist Neil Turok, executive director of Perimeter Institute, a quantum physics think tank set up by Research in Motion co-founder Mike Lazaridis. Prof. Turok has seen even more direct pressure applied to British scientists in recent years. "The meter has moved."

What many governments seem to have forgotten, adds Pekka Sinervo, senior vice-president of research for the Canadian Institute for Advanced Research, is that developments in applied research are always built atop layers of non-commercial discoveries, instructive mistakes and scientific tangents.

From his perspective, Prof. McNaughton feels the problem stems from a lack of public understanding about the meandering nature of scientific inquiry. Without a foundation of basic knowledge, he says, the "pyramid falls over. When an advance occurs, no one ever tracks the history of how we got there."

During the 1940s, a German scientist named Peter Holtz began to experiment with the behaviour of a chemical relative of dopamine, known as L-dopa. Meanwhile, other scientists at Cambridge University in England were investigating the physiology of these substances and how they affected the brain.

Meanwhile, a young Swede named Arvid Carlsson enrolled in medical school, determined to go into research. He studied pharmacology and the way sedatives work. Later, as a postdoctoral student, Dr. Carlsson began probing the reasons why some compounds lower heart rate and blood pressure, drawing on other researchers' earlier insights gleaned about the physiological effects of dopamine.

Soon, he returned to the University of Lund, in Sweden, to set up his own lab. There, he decided to further push his results, eventually concluding that administering L-dopa to sedated rabbits could make the animals alert. That result, in turn, led him to investigate how dopamine behaved in brain tissue, especially those areas related to movement. In 1958, Dr. Carlsson and a colleague discovered that dopamine was a major neurotransmitter. Forty-two years later, Dr. Carlsson received the Nobel Prize for shedding new light on how the brain functions.



Scientists operate in a world dominated by experiments, collaborative projects and question marks. Every paper contains a conclusion, proposals for follow-up studies, and a streamer of citations. Researchers measure their own intellectual status in terms of the number of citations their papers garner. In this way, shards of knowledge are relentlessly cascading into the work of other researchers.

Indeed, the recombinant logic of scientific inquiry is inherently unpredictable, notes Prof. Sinervo, a University of Toronto physicist. "You don't know," he shrugs. "If you knew what the answer is, you wouldn't have to ask the question."

In his own field, Prof. Sinervo has secured grants worth $40-million for highly intricate, decade-long experiments on the nature of proton collisions. He jokes about "deferred gratification," but acknowledges a reality of his line of work. "In my lifetime, I don't anticipate that the knowledge that comes out of these questions will have immediate benefit to society."

He has, however, observed the strange magic of serendipity from close up. More than 20 years ago, physicists in his field needed ways to share documents because they were working in so many different places. To solve that mundane logistical problem, they designed network software that would one day become the World Wide Web.

After Dr. Carlsson made his dopamine discovery, scientists and graduate students in London, Japan and Montreal began to measure depressed dopamine levels in Parkinson's patients and animals. Some developed techniques for mapping the chemical's travels through the brain. In 1960, a clinical neurologist in Vienna decided to try injecting L-dopa into Parkinson's patients, with "dramatic but transient benefits in these patients, heralding the beginning of the era of L-dopa therapy," according to Stanley Fahn, of the Neurological Institute in New York.

The accumulation of all the knowledge that leads to significant breakthroughs will often take place in several countries, over many decades, and under the purview of public universities, government agencies and privately operated research labs.

Prof. Boyle, for his part, was an alumnus of the legendary Bell Labs in New Jersey, an institution that no longer exists. It's not the only private research facility that has gone the way of the dodo. Xerox had its own ambitious pure research operation, as did Canada's Northern Telecom.

Both are now gone, although other private research hot- houses - such as the Perimeter Institute or Google.org, the search engine's R&D shop - have cropped up, thanks to wealthy entrepreneurs with private passions.

Prof. Turok believes an unfettered research agenda coupled with private funding is a "powerful combination." The Perimeter scientists, he says, feel a "huge responsibility" to drive the scientific agenda envisioned by their patrons.

But Prof. Sinervo points out that such institutions will never provide sufficient support. "It's not sustainable to expect the private sector to invest significant resources into fundamental research. Then it becomes a question of how much should government see [fundamental research]as its primary role."

And therein lies the policy riddle. Lawyer-philanthropist Richard Ivey, who chairs the CIFAR board, observes that Canada is "at risk in the medium- to long-term" because of the exodus of manufacturing and the limitations of resource industries. Some policy-makers clearly feel the pressure and want researchers to be providing the building blocks for Canada's economy in the 21st century.

"In my experience," Neil Turok says, "if you look back in history, the greatest wealth has come when people are free to pursue their own ideas and aren't constrained by a predetermined agenda."

During the early 1960s, the development of the drugs now used to treat Parkinson's evolved by trial and error, with some scientists trying higher doses and others finding no benefits at all. By 1967, a researcher stumbled upon a dosing technique that achieved predictable therapeutic results. It's still in use today.

Since then, neuroscientists have learned even more about dopamine's role in treating drug addiction and compulsive gambling. As for Henry Wellcome's free-wheeling lab, it eventually became part of GlaxoSmithKline, the world's second-largest drug company.

"Name me a major recent clinical or technological breakthrough in neuroscience," muses Prof. McNaughton, the brain chemistry researcher, "and I'll show that it has its foundation in curiosity-driven research by people that are mostly retired, if not dead."

In all likelihood, they weren't using business plans, either.

John Lorinc is a freelance writer in Toronto.

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