Back to Basic

By Lisa Willemse; co-published at www.medium.com/the-expression

Today’s research environment has a strong emphasis on translation to new technologies and treatments. But we wouldn’t be here without basic research and tomorrow’s advances will continue to rely on the fundamental understanding and discovery it brings.

On a good day in the Andras Nagy lab at Mount Sinai Hospital in Toronto, 20-25 different students and staff will stop in for anywhere from two to 10 hours to do the kind of work typical in any stem cell research laboratory – feed cells, observe activity, record results, write papers.

Nagy calls himself a basic researcher – this is where his heart lies, in the search for answers to fundamental questions of biology – yet only about half of the work that transpires in the lab falls into this category. The rest is considered translational research, which has a much more explicit goal in mind: solving key problems to pave the way for new treatments or enabling technologies.

This same kind of dynamic is also the norm in Frank Beier’s lab at Western University in London. And, in fact, at most other basic research labs in Ontario.

To the casual observer, research is research and there is little visible difference between culturing cells to learn about their behaviour versus using them to test reactions to a new drug. Ultimately, we trust that all of it will lead to better health and living.

The reality is that research has become so much more sophisticated, high tech, and fast – and this is a good thing. The fact that half of a stem cell researcher’s work now includes translational aims means that we’ve amassed the necessary knowledge to push forward and realize the promise of regenerative medicine. The progression to this was both purposeful and inevitable, given the immense amount of research activity we’ve seen in the past few decades, not just in Ontario, but in Canada and across the globe.

“The early 2000s saw the creation of the Canada Research Chairs, Canada Foundation for Innovation, and Genome Canada, and this drew a lot of fantastic researchers to the country. With these and other programs, we developed tons of tools that were unimaginable even 10 years ago,” says Beier, whose focus is on skeletal physiology, including bone and cartilage development and osteoarthritis.

One of the other products of these programs is the wealth of research talent: young, highly-trained professionals who are taking jobs not just in research, but in business, communications, and a range of other fields. Paul Krzyzanowski is one of these new hybrids emerging from basic science labs, currently combining a postdoctoral fellowship at the Ontario Institute for Cancer Research with concurrent MBA studies at the Rotman School of Management at the University of Toronto.

“The wealth of tools available in biology puts us on the verge of a big evolution in healthcare,” Krzyzanowski says. “We can now collect and analyze vast amounts of information about human and pathogen movements, monitor cancer and diseases at the microscopic level, and manipulate the human body in more sophisticated ways using drugs, biologics, or cell therapies.”

But while statements like these, and indeed, people like Krzyzanowski make it tempting to put all of our energies into translation, we don’t want to ditch basic research. Not now. Not ever.

Basic research might well be an unsung hero, but it is still critically important to our innovation engine.

Successful basic research requires a fine balance between unfettered curiosity and careful management of outcomes and public funds.  Such a balance often leads to unexpected discoveries that can have immense impact on future directions – the identification of stem cells from experiments on radiation being just one notable example.

“I think that overall, the emphasis is positive. Many historical advances in biomedical sciences were translationally driven – for example, the development of insulin and the polio vaccine – and I think new science must be translated into commercial use in order to capture public awareness and actually serve the public interest through better technologies,” says Krzyzanowski.

“In order for a new discovery to be widely adopted it first needs to be turned into a product, whether it’s a commercial product or an academic one like a publication or a piece of open source software. Whether these are made for-profit or not is another debate, but I think good scientists and trainees keep a product-focused mindset,” Krzyzanowski adds.

But, as vital as translational research is, commercializable products cannot be the only goal. “Research funders need to be careful that they don’t over-promote commercialization to a point where basic researchers start relying on projects with limited potential or aren’t disruptive,” cautions Krzyzanowski. “There definitely needs to be a foundation of basic research with little guarantee of a commercial payoff, but we need to be judicious in how basic research resources are spent.”

Perhaps more importantly, we simply don’t have all the answers yet. Increased and more exact knowledge will inevitably lead to more cost- and health-effective products and therapies.

“In the end you need to understand the underlying biology,” says Beier. “You have to understand how an organism works when it’s healthy in order to then understand the first things that go wrong when there is disease. Only that will lead to an appropriate treatment to attack the cause of disease, rather than just the symptoms.”

In his lab located a short drive up the 401, Andras Nagy agrees wholeheartedly with this assessment. “There are many, many things for which we are just not ready to think about translation. There are basic questions that have to be answered and we can’t wait for others to do this research – the reality is that it just might not get done,” he says.

For Nagy, this means a comprehensive understanding of what a cell goes through during reprogramming – for example, the gene expression, the DNA structural changes, what’s happening on the cell surface, the proteins that are present. It’s an understanding that will be fundamental to future treatments developed with reprogrammed cells, such as those that were used in the landmark clinical trial in Japan, now halted in part due to unexpected cell activity. Nagy embarked on creating this roadmap of cell reprogramming a few years ago, as part of a large, multinational effort that has netted seven important papers. And they’ve only scratched the surface of the data set – a wealth of knowledge that could help define treatments and reduce the cost of their development is yet to be analysed.    

“We are in a very exciting time. There are major revolutions happening in our understanding of life, of biology and in transformation of medicine."

The funding environment is still challenging – and changing – but we stay optimistic that the excitement we currently have will attract the right programs and people to move ahead.”

Image credit: Jayeson Earl