Ontario - A Leading Centre Of Stem Cell Research That Is Building A Foundation Of Promise

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By Rob Ireland

While empirical scientific study may belong to the world, Ontario - through research and innovation - has earned the right to be called the home of stem cell research.

It was stem cell pioneers James Till and Ernest McCulloch of the Ontario Cancer Institute in Toronto who issued a research paper in the early 1960’s in which hematopoietic (or blood forming) stem cells were first described. In September of 2005 – nearly 40 years later - this pioneering research was formally recognized when Till and McCulloch were awarded the prestigious Lasker Award for Basic Medical Research. The Albert and Mary Lasker Foundation characterized their research as having “…laid the foundation for all current work on adult and embryonic stem cells and transformed the study of blood-cell specialization from a field of observational science to a quantitative experimental discipline.” The award duly recognized work that gave birth to a new way of approaching human tissue research, and moreover, medicine as a whole.

Since those auspicious beginnings, Canada continues to be ranked in the top six countries worldwide for its ongoing leadership in stem cell research. In an industry briefing regarding regenerative medicine released in January 2008, (authored by Litinski and Kim), Canada was ranked 1st globally with respect to its world-class scientific research. Within that briefing document, it was also noted that roughly one third of all stem cell researchers are from Ontario. It is therefore of no surprise that along with Quebec, Ontario consistently ranks in the top five regions in North America for stem cell research.

A promise unfulfilled

Stem cell research has since branched out into many discrete and exciting fields of study and provides a potential cure for many orthopedic applications, most major heart and neurodegenerative diseases, wound healing and even most forms of cancer.

Additionally, it provides an ability to study human biology and disease in laboratory models that are otherwise inaccessible and ethically impossible. The ability to study human tissue lines under laboratory conditions has almost limitless ramifications upon both pure and applied research for drug testing and development.

With the prospect of providing such a panacea for human healthcare, stem cell research has also been the source of one of the most polarizing ethical debates ever to be associated with a scientific endeavor.

For years, the primary concern of scientists (and even the general public) has been that the source of stem cell tissue was human embryos and (cadaveric) fetal material. The issues, which are argued on medical, ethical, religious and legal grounds ‘bleed’ into other contentious debates such as the beginning of human life and at which stages it should be protected. The result has been the creation of a loose and emotional public forum in which Hollywood actors play their part, elections are won and lost and people with half the facts feel as though they are well informed. The net result of this medical and ethical ping-pong is the fact that stem cell research is subject to often arbitrary funding, regulatory and legislative constraints and thereby restricting the potential for disease research and the development of regenerative therapies.

Induced Pluripotent Stem Cells – separating vital research from an ethical dilemma

In 2007, Dr. Shinya Yamanaka and his colleagues discovered a technique to create what are now known as human induced pluripotent stem (iPS) cells and by definition, produce all the cells of the adult. By introducing a blend of genes and specific transcription factors into fully differentiated adult cells, Dr. Yamanka found that a pluripotent state could be induced such that iPS cells behave like embryonic stem cells.

The significance of Dr. Yamanaka’s breakthrough is that it effectively eliminates the ethical debate surrounding stem cell research by inducing an embryonic cell phenotype from adult tissue. It is entirely possible that through this research, fetal tissue will no longer be required to generate stem cells and therefore two significant hurdles are simultaneously overcome. The technique eliminates the need for embryonic tissue sources and it accelerates the onset of potential regenerative procedures in humans by negating any autoimmune or rejection issues. In the near term, the generation of iPS cells from patients can be used to study hereditary disorders and identify new drugs to treat a whole host of diseases.

Ontario – carrying on the tradition of world-class Stem Cell Research.

In the tradition of Till and McCulloch, Ontario continues to be the home of scientists that are global leaders in stem cell research. Of note are people like Janet Rossant, a stem-cell network investigator with the Hospital for Sick Children and the world’s second ranked researcher based upon papers published and citations of her work.

Ontario is also home to Dr. Gordon Keller the director of the McEwen Centre for Regenerative Medicine at the University Health Network in Toronto – a scientist who has recently shown that that Ontario-based research continues to shake the world’s scientific community. On April 23rd, 2008, Dr. Keller and his team announced that they had grown human heart progenitor cells from embryonic stem cells. The announcement is of global significance due to the new ability of laboratories to produce human cardiac tissue for study within the development and testing of new drugs. It also provides a source of tissue that may provide new ways of treating human hearts damaged by heart attacks.

In fact, Ontario is blessed with a number of world-class scientists that are working on various aspects of iPS cell research, including; Bill Stanford (University of Toronto), James Ellis (Hospital for Sick Children), Ben Alman (Hospital for Sick Children), Freda Miller (Hospital for Sick Children), Andras Nagy (Samuel Lunenfeld Research Institute at Mount Sinai Hospital), Peter Zandstra (University of Toronto), Julie Audet (University of Toronto), Derek Van der Kooy (University of Toronto), Mick Bhatia and Jon Draper of McMaster University and Michael Rudnicki of Ottawa Health Research Institute.

Ontario – understanding and nurturing its ultimate competitive advantage - collaboration

But why has Canada become one of the top six stem cell research nations globally? And why is Ontario such a driving force of its own? The key is its culture of collaboration.

Supporting Canada’s competitive position is Aggregate Therapeutics, an organization created by the Canadian Stem Cell Network, which provides a national research coordination capability that can “pool or bundle intellectual property, achieve critical mass and generate commercial benefit in stem cell research.” The Canadian research community is also supported by MaRS – a non-profit organization that has collaboration between businesses, scientists and venture capitalists as its sole purpose.

But structure alone does not create collaboration. Such a culture cannot be forced or mandated; rather it can only be supported and nurtured. It is the scientists themselves who have created their own, informal collaborative network because they know that it is the best way to sustain leading edge research. Ontario has organically developed a highly collaborative community of stem-cell researchers and that culture is unique within such a highly competitive field.

Shared intellectual capital is
the key to Canada’s future role in the global innovation agenda

For Canada to continue to be a recognized centre of stem cell research, it must both create its own world-class facilities staffed with world-class researchers AND continue to leverage its rich history of collaboration. The Canadian government won’t be able to outspend many other nations, but its ability to attract the best and brightest, and its rich history of collaboration, will make Canada a fulcrum against which other research can be fully leveraged. Within Canada, Ontario is of particular note because it has created the Ministry of Research and Innovation (MRI) and the only province with a Ministry with such a focus. Beyond simply providing funding, MRI Minister John Wilkinson recently stated “that it is up to all of us to recognize and encourage Ontario’s key global competitive advantage - our culture of collaborative research.”

In May of 2007, Dalton McGuinty, Premier of Ontario, and Arnold Schwarzenegger, Governor of California, met and agreed to back promising new stem cell research that would help uncover new therapies for cancer.

California is a leading region for stem cell research in large part due to the establishment of the California Institute of Regenerative Medicine (CIRM) and its commitment to provide US$3 billion in targeted funding over 10 years. Such a high-level inter-regional commitment to collaborate established a basis on which stem cell research could accelerate.

The Challenge for Canadian
Research – a shared objective for the public and private sector in Canada

In Canada, world-class researchers routinely work together on common goals and this spirit of collaboration is perhaps best exemplified within the field of stem cell research. Canada’s culture of ‘collegial collaboration’ is often the biggest reason why the best minds locate in research hot-beds like Toronto. To continue to compete and win globally, facilitation of international collaboration will be the linch-pin to Canada’s success.

Canada’s emerging place on the world stem cell stage as a contributing partner within leading edge research is the position to which all regions should aspire. It is the only rational way to fully pursue a complex and diverse, yet interconnected field of stem cell research. Within any highly competitive research field such as that defined by iPS cells, regions and researchers must be prepared to move quickly and decisively to create collaborative partnerships and research sharing partnerships – not trying to own the science but share the exploration of an important research field.

Finally, we must remember that both pure and applied research needs to be supported vigorously throughout Canada. While much of the ongoing iPS research will lead to commercially viable medicine and therapeutics, the pure research on which all subsequent stem cell research was built, cannot be forgotten. Till and McCulloch could not have imagined the extent and direction of today’s stem cell research – a path that first started in Ontario. It is on the foundation of publicly funded pure research that future breakthrough applications will be built, and through the collaborative spirit of our world-class researchers that Canada’s leadership position can be maintained.