“Ladies and gentlemen, we invest in science and technology for two reasons: to create knowledge and to exploit that knowledge for social and economic gain. Unfortunately, all too often the knowledge gained is opportunity lost.”
-The Honourable Gary Goodyear, Minister of the State for Science and Technology
Last issue, we reported on how translational research is on the rise. This issue we offer an in-depth look at the importance of supporting basic science research in a balanced national science policy, and the unsettling trends in Canadian science funding that are moving too far in one direction.
Gary Goodyear’s words summarize the current dilemma in Canadian science policy – a shifting of priorities and funds abjectly favouring the commercialization of scientific research. Indeed, there are clear benefits to supporting applied or translational research, including indirect effects of stimulating the economy after a troubling recession. However, we cannot afford to support innovation and translational research at the expense of basic science, which is how the current government has prioritized spending in research and development (R&D).
Basic science: The bread and butter for a knowledge-based economy
Applied research improves and saves lives on many levels, but basic research is the bedrock for such innovation and application. The technologies that enable you to flip through this article on your tablet owe their existence to a few scientists tinkering with solid-state technologies at Stanford University in the latter half of the 20th century. Such fundamental research led to Bell Laboratories and the Silicon Valley boom, which in turn gave rise to microchips and wireless communications. The race to the moon and the sending of instruments beyond the edge of our own galaxy have also brought us such earthly pleasures as memory foam mattresses, enriched baby food, and even invisible braces.
In the biological sciences, seminal studies in the fly (D. melanogaster), the worm (C. elegans), a mustard weed (A. thaliana) and the sea urchin (S. purpuratus) have established the foundation for our understanding of genetics, development, RNA interference and cell-cycle control. The discovery of these core concepts and pathways are the backbone supporting studies of human disease. Take almost any drug on the market, and one can trace it back through decades of discovery-based research.
Two such examples are Vismodegib and Gleevec. Vismodegib was approved in early 2012 for the treatment of inoperable basal cell carcinomas. It is one of the first class of FDA-approved drugs that works by inhibiting the hedgehog (HH) signaling pathway. Where was this pathway first identified? In the fruit fly, circa 1970. Drosophila biologists Christiane Nüsslein-Volhard and Eric Wieschaus were originally interested in how a fruit fly egg develops into a complex animal. They identified a set of genes, including HH, which controlled the organization and emergence of fly body parts. They shared the 1995 Nobel Prize with Edward Lewis for their collective work in the genetic control of Drosophila embryogenesis. Almost two decades after the discovery of HH signaling, it became clear that overactive HH signalling was common in several cancers, most prominently in basal cell carcinoma. Research directed at blocking parts of the pathway successfully translated into clinical trials and ultimately, a drug on the market.
Gleevec is another cancer drug, and owes a large part of its existence to Tony Pawson, a scientist who was based at the Mount Sinai hospital in Toronto. In his student days in England, Pawson was fascinated by how cells communicate and respond to signals from their environment. He started looking for single proteins that could change the entire organization of a cell, and stumbled upon work involving the Rous sarcoma virus, a chicken retrovirus that causes tumours in chickens. Virus-infected cells had a mutated, overactive version of a protein called Src, which was later identified as a tyrosine kinase (a protein that adds a phosphate group to itself or another protein). Pawson compared phosphorylating enzymes from other sarcoma viruses and human cancers, and eventually identified the Src Homology 2 domain (SH2). Work from his lab revealed that the clustering of cell surface receptors mediate phosphorylation cascades through SH2 domain binding, transmitting environmental signals into a defined change in cellular behavior. In cancer cells, mutated receptor proteins can transmit a continuous signal, leading to uncontrolled growth or metastasis. The understanding of these core concepts culminated in one of the most successful cancer drugs of all time – Gleevec. Gleevec works by blocking the activity of a tyrosine kinase called BCR-Abl in cancer cells. Clinical trials for Gleevec began in 1998 and the drug received FDA approval in May 2001, well over 30 years after Pawson found his inspiration in a “funky chicken virus”.
So, akin to a strenuous mountain climb, translational research is the view from the top, but it is only made visible by the knowledge and experience gained from the long ascent. Take away that foundation, and decades from now the Canadian innovation in industry and health sectors will be about as successful as Monty Python’s attempts to scale the twin peaks of Kilimanjaro. As the late Pawson had explained after receiving the Kyoto Science prize, “It would have been hard to predict that work on a curious chicken virus would have ultimately led to new ways of thinking about how human cells are organized, and to new drugs to treat one of mankind’s most persistent enemies […] Basic science [is] a long-term investment that will yield completely unexpected dividends for humanity in the future.”
Long-term investment versus short-term gains: Are we tipping the balance irreversibly?
Basic science has huge benefits to society, but long-term government funding is the only reliable option for sustaining discovery-based research. The private sector has traditionally supported more short-term, application-based R&D, as these projects are usually of lower-risk and higher immediate gain than discovery-based research.
The problem arises when governments follow the private sector in placing all the emphasis on the D side of R&D. Indeed, politicians want the credit for putting tax dollars to the best use within their own terms of office. While scientists understand the risks and benefits of exploratory research, the expectation for instant gratification and quarterly-profit perspectives of most politicians and voters often preclude their support of long-term scientific investments.
The statistics demonstrating this point are all too chilling; despite pledges to add $37 million in 2013-2014 funds to the tri-research council, most of the funds will be re-allocated to short-term industry related grants and programs. Moreover, the base budgets for the main science funding agencies in Canada, the Natural Sciences and Engineering Research Council (NSERC) and Canadian Institutes for Health Research (CIHR), have actually decreased by roughly 7% from 2010 levels when adjusted for inflation. Funds for Discovery Grants and other basic operating grants have also decreased by 11% while funds allocated for “research projects and network activities intended for socioeconomic impact” rose by almost 23%. Altogether, only 20% of the operating budget of the National Research Council (NRC) will fund “curiosity and exploratory activities”.
In sum, the current administration’s policies on scientific discovery and innovation, if left unchecked, could permanently damage Canada’s knowledge-based economy, because the benefits of long-term investments are two fold:
1) There is a constant broadening of the knowledge base, led by basic exploration and discovery
2) Long-term funding by way of operating grants is the only way to support the constant training of new scientists
The answer here isn’t to fund all scientists who write grants, but severely limiting the support of good basic science isn’t the answer either, for many reasons. When success rates for regular CIHR operating grants have fallen from over 20% in 2006-07 to 8.7% for 2012-13 despite maintaining similar levels of “fundable” grants as judged by peer-review, scientists will start voting with their feet. Taken together, these funding decisions put Canada in danger of losing both a broad base of knowledge and an entire generation of future big thinkers.
Where do we go from here?
How can we expect to be so entitled to an unbridled, creative scientific freedom if there is no national appreciation of its value in society? Perhaps it is time to change the scope of our conversation, and how our work is perceived. We must shift public understanding of the risks and benefits of basic science and of the joys of discovery if we hope to sustain our own explorations.
Unfortunately, most researchers would rather bathe in concentrated hydrochloric acid than trade in their pipets for a seat at Queen’s Park or Ottawa. Scientific martyrdom aside, something has to be done if we have any chance at implementing significant policy changes. Fortunately, thousands of scientists recently took a step back from the bench to highlight these issues in public. A series of “Stand Up for Science” protests organized by the Ottawa-based science advocacy groups Evidence for Democracy and Scientists For the Right to Know took place across the country on September 16, 2013. Thousands of scientists and supporters marched in Toronto, Ottawa and 15 other cities in Canada to make the case for reformed funding structures and public access to science. These events are capturing public attention on the role of science in society and the problems it faces under unbalanced funding structures. Science advocacy groups host policy debates between MPs for the public to attend, and help draft scientifically informed motions set forth in Parliament. At even the smallest levels, we can do the same.
So as a scientist, if a picket sign is too much, pick up a pen. Write to your MPs and get the message heard! Attend town halls, local election debates and school budget meetings to give comprehensive science research and education a stronger voice. Engage the public by volunteering for science advocacy groups or events, such as those mentioned earlier, or Let’s Talk Science (LTS). LTS programs engage students at all levels to spark their scientific curiosity and brings the conversation home to their families. The immunology department’s SciChat Adult Outreach group makes topics such as vaccines and drug development accessible to the adult layperson and provides a forum for informed discussion.
Overall, the public and politicians alike need to be engaged on the importance of both basic and applied research, and to be aware that much remains to be discovered about the basic mechanisms underlying cellular and animal processes. As researchers, it is important to be curious about a scientific phenomenon, even if it’s not immediately relevant to a specific human disease. Despite the overall climate, good science still gets funded at some level. Translational and applied research is important and the development of new treatments and technologies would not happen without it. However, if the fundamental questions still keep you up at night, I implore you not to turn off the lights. Not just yet. Basic science is a crucial part of a productive research program, and its future is only possible if we continue to give it the public attention it deserves.
I would like to thank Michele Anderson, Jonathan Rast, Stephen Rubino, Vineet Joag, and many friends and colleagues in the Department for stimulating discussions on the topics at hand. We invite you to share your thoughts with us below.
Canada Budget 2012 and Budget 2013
SSHRC, NSERC, and CIHR Departmental Performance Reports
NSERC 2013-14 Report on Plans and Priorities
OECD (2013), OECD Factbook 2013: Economic, Environmental and Social Statistics, OECD Publishing. doi: 10.1787/factbook-2013-en
Assumptions based on inflation from 2010 dollar levels.
Tony Pawson’s eloquent Kyoto Prize acceptance speech in support of basic science: http://www.inamori-f.or.jp/laureates/k24_b_tony/img/lct_e.pdf
For more information on grass-roots opportunities, check out http://getscienceright.ca
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