Ernest Cutz is Professor Emeritus of the Department of Laboratory Medicine and Pathobiology at the University of Toronto, and a former senior pathologist in the Department of Paediatric Laboratory Medicine and Senior Research Associate at the Hospital for Sick Children’s Research Institute.

 

This year’s Nobel prize for Physiology and Medicine, awarded to Drs. William Kaelin, Gregg Semenza and Sir Peter Ratcliffe for discovering details of how the body’s cells sense and react to low oxygen levels, is a remarkable feat for several reasons. The Nobel Committee cited the discoveries as ”one of life’s most essential adaptive processes”. The laureates’ research answers profound questions about how the body works, helping to inform potential new therapeutic targets to treat cancer and other diseases. While I rejoiced in this remarkable accomplishment by these exceptional clinician-scientists, I was reminded of a colossal failure of the grant review process for medical research funding in Canada.

During my 40 year career as a clinician-scientist, I worked in the field of oxygen sensing and was part of the team that discovered the role of pulmonary neuroepithelial bodies (NEB’s) as hypoxia-sensitive airway sensors. Until recently, our research efforts were funded by grants from the Canadian Institutes for Health Research (CIHR). These grants allowed us to make great progress, including the discovery of a unique NEB cell based oxygen-sensing mechanism relevant to paediatric lung physiology and various pulmonary disorders. We also developed a number of collaborative projects with scientists in Canada and abroad, which included working with Sir Peter Ratcliffe and his group at Oxford University, UK.

In 2015 we submitted a grant application to CIHR entitled “Pathobiology of pulmonary neuroendocrine cell system in paediatric lung disease”. In addition to being highly original and relevant to human disease, this application included several important pilot studies that supported our hypothesis as well as supporting the feasibility of proposed experiments. It was also backed by collaborations with several world- class scientists such as Sir Peter Ratcliffe (Gairdner award, 2010; Nobel laureate, 2019).

Our team was shocked and disappointed when CIHR deemed the application not competitive and rejected it. In fact, it was rated so low by reviewers that it was not even deserving of extended discussion or a Scientific Officer’s note. The two reviewers who assessed our application noted it as superficial and carried out by unqualified individuals. Our letters of complaint to CIHR officials went largely unacknowledged. We felt that we were victims of a flawed and dysfunctional grant review process. The loss of funding had grave consequences such as the closure of our lab and the subsequent loss of highly qualified personnel.

However, we are not alone in this predicament as other research groups have been similarly affected. At the time, due to widespread dissatisfaction expressed by the medical research community, CIHR promised to re-asses and update their grant review procedures. As a result, a special panel with a mandate to devise a more fair and equitable review process was established. Despite claims of wide consultation with the research community, many worry that this has created more bureaucracy. A simpler solution such as the development of an appeals process that includes an independent re-assessment to resolve discrepancies or disagreements (as is the case with other granting agencies) was not considered. While CIHR’s attempts to improve the quality of reviews is laudable, it’s not clear that their newly created ‘College of Reviewers‘ includes sufficient medically qualified clinician-scientists to provide evidence-based input.

Hence, I am not optimistic that our experience will not be repeated in the future with a “Nobel prize“ quality research proposal with true potential to promote and advance innovation and facilitate scientific discoveries being rejected.