Dr. Bruce McManus — Institute for Heart + Lung Health & PROOF Centre

Given Providence's affinity for exploring the undefined realms of medicine (think TAVI, telehealth, breakthroughs with HIV/AIDS, etc.) it's not surprising that some of the world's most innovative work in the field of personalized medicine, molecular markers and genomic testing is being done at PHC.

Providing physicians with infallible information regarding a patient's unique genetic profile, personalized medicine opens the door to a patient’s predisposition to certain diseases, allergies to certain medicines and sheds light on a treatment plan that allows for more aggressive therapy to slow disease progression.

Pretty awesome stuff, right?

Meet the man helping to lead the charge, Dr. Bruce McManus, MD, PhD, FRSC, FCAHS, professor, UBC Pathology and Laboratory Medicine Department, co-director, Institute for Heart + Lung Health and CEO, Prevention of Organ Failure Centre of Excellence (PROOF Centre).

Before we get started, we likely need to define a few things to get everyone on the same page.

What’s the best definition you’ve heard for “Personalized Medicine”?
Funny you should ask. This is an important issue, which leads to various levels of confusion.

I actually don’t like the term ‘personalized medicine’ because it is a very limiting definition that focuses on the ‘right drug for the right patient in the right dose at the right frequency and at the right time.’ Thus, it’s largely focused on drug therapies and aligned with the pharmaceutical industry.

There is another commonly used term, recently heard again in President Obama’s fiscal allocation for ‘precision medicine,’ which is often spoken of as P4 Medicine: predictive, preventive, personalized and participatory. But, P4 Medicine is also about ‘precision’ and ‘partnerships.’ So, there are several additional P’s that must be included if we’re talking about a new era of health care that includes medicine. And, one of the P’s might be very precise but entirely inaccurate, which makes precision medicine an incomplete concept.

Finally, there are at least two other key elements that are de-emphasized in either personalized or precision medicine:

Physicians have been trying to be personalized or individualized in their delivery of care for centuries. It’s simply that we now have new data sources, like the genome, to make things potentially much more personalized.
Personalization requires consideration of the elements that impact health, risk or disease across a lifetime. Together, environment (social, economic, ethnic, physical, etc.), behaviour (exercise, diet, sleep, life-balance, etc.) and genes are the elements that together underpin personal health and our approach to health care.

So, while it’s not a term used by others (yet), I like to speak of ‘person-specific health care’ because it can embrace all of the elements important to health and care. We have a range of data sources and analytical tools, if applied in an integrative fashion, can effectively bring all of the relevant information into play for patients and their caregivers.

And how do you define a biomarker?
Biomarkers are biological markers are weathervanes that predict, diagnose, or prognose risk or disease. They can also forecast given patients’ responsiveness to standard of care drug therapies or other care interventions.

These weathervanes can be molecules measured accurately, precisely and reliably in any body fluid, cell or tissue. However, given that the bloodstream is a freeway that is often sampled in clinical laboratories — where the biology or pathology of various organs and tissues can be reflected in peptides, proteins, RNA or metabolites — many people searching for markers as more specific and sensitive blood tests can scour the blood and its compartments, like plasma and white cells.

The goal is to obtain and validate signatures which, just like your handwriting, your fingerprints, or your retinal scan, reflect YOU. The passion for finding better biomarkers or “magic markers” is driven by the desire to help patients, lessen our invasion in their bodies, reduce costs and allow as much care as possible to be delivered near home, with primary care physicians.

Ok, thanks for getting us up to speed. Now onto questions about how you found yourself involved in person-specific health care.

You’re an alumnus of the University of Saskatchewan — what was it about the programming/professors/campus at U of S that drew you there?
I grew up in an era when you went to your nearest university, and I grew up in Western Saskatchewan. So, pursuing my first degree at U of S was really a geographic accident. But as it happened, there was an amazing array of professors in a range of domains I was interested in like Chemistry, Sociology and Physiology.

For my Medicine degree, it was about being close to my children’s grandparents and it turned out that the undergraduate medical curriculum was strong at U of S as well. I especially remember my teachers in Pharmacology, Electrocardiology, Neonatology and Surgery.

U of S was a great place to learn and when I pursued studies at several other universities in the USA that foundation really helped me in so many ways.

What did your journey to person centred health care look like?
I have always been interested in human health, whether as determined by behaviour and environment, or our biology. And with my broad experiences in the life sciences and medicine I really think I was, along with many other people, on a voyage towards more patient-specific care over the past decades.

But things really changed for me when I pursued a sabbatical experience at the Max Planck for Biochemistry in Martinsried, Germany. I was engaged more heavily in molecular sciences after that, and we did a lot of work in the past 20 years on the signals that control the fate of cells or hosts in inflammatory diseases like allograft rejection (the rejection of tissue transplanted between two genetically different individuals of the same species) and virus infection of heart muscle.

I was really lifted and inspired by my many trainees, the vast majority of whom brought raw brilliance to the laboratory or clinic, and then pushed for answers that touched on issues underlying patient-specific risk and disease.

My many professional colleagues have made this blending of classical medicine, physiology, molecular sciences and computation an incredible experience!

What’s it like to discover a biomarker?
Biomarkers have a magical impact on the team!  Everyone from the patients to the caregivers to the scientists and our many partners are inspired to push harder, to move these precious products into the clinic or into industry. 

We are reassured that bringing the power of modern science to better health care really is possible, and that we can play a part. What a luxury of opportunity!

How long have you been in the active pursuit of biomarkers?
I guess I never called them biomarkers until the turn of this century, but we have been interested in biological markers of risk and disease in humans and other model systems for quite a time.

Our first formally named large-scale initiative, funded competitively by Genome Canada, was Biomarkers in Transplantation beginning in 2004. It’s been a tsunami since then!

The key is to validate biomarker sets such that they can potentially become clinically useful, high-value laboratory tests, or guidance tools for drug development organizations.

What is it about the combination of COPD and biomarkers that excites you the most?
Well, first and foremost, this ‘work’ is a privilege: working with a full gamut of colleagues to try to provide tools that can help many, many patients and their caregivers.  And since COPD is such a huge global burden, much like heart failure, getting laboratory tests and biomarker signature guidance that can immediately improve care and also spur drug development in a more rational and effective way is simply something I didn’t grow up thinking was plausible. And here we are doing it!

Find out more about Bruce’s work around developing prognostic and diagnostic biomarkers for better management of COPD exacerbations.

What is it about the culture at St. Paul’s that made you want to make it your home?
I arrived at St. Paul’s and Providence somewhat by accident in 1993, when regional planning had suggested that the advanced heart care should be located at St. Paul’s. I was to serve in a research leader capacity and a cardiovascular pathology diagnostics capacity.

The Dean of Medicine and the CEO of St. Paul’s were very, very supportive in getting me set up so I could participate in the programs of research and care at St. Paul’s.

Jim Hogg and the respiratory research team had built a great foundation on which we were able to conceptualize a future of heart and lung, which has escalated throughout the community. And from those first steps, things have grown like wild-fire.

When did you realize that personalized medicine was the future of medicine?
Interesting question! I guess we knew we could be more patient-specific in looking at molecular responses to virus infection in the late 1990s. This catalyzed thinking about computational sciences as a pivotal foundation for future advances, and led to the Genome Canada-funded work I mentioned earlier. 

Things escalated with the creation of the PROOF Centre of Excellence in 2008, and added to that is the wave of efforts from around the world to harness molecular knowledge about DNA — and also about RNA (ribonucleic acid), proteins and metabolites — in a sophisticated fashion, while extracting sign-post simplicities that can arise from the extraordinary complexity of a human being.

Your list of accomplishments is long. What accolade puts the biggest smile on your face?
I don’t really think about all of that. If you’re lucky enough to live long enough and you keep going, persisting, then people appreciate the few things you eventually deliver.

In the end, it all requires a team, and most of the things for which a person is recognized for are a reflection of the “village” of talent and focus arising from the team. I have been on a lot of good teams with good coaches. Mentors make magic happen.

What is your next big goal on the horizon?
To help get the advanced diagnostics laboratory operational at St. Paul’s Hospital is a major short-term goal.

With a little luck in the coming weeks, we will have the money and momentum to make it happen. Again, it is about great people in the clinical laboratory with whom we share a vision for transforming the precision and accuracy of testing for risk and disease through the power of highly discriminative blood tests. Coming soon!

What does success look like for you?
Professionally, it would be that Providence Health Care moves boldly, beyond conversations and planning, to more doing.

It means being fast on our feet in assuring that the organization can and does attract and nurture the very best young talent in science, health care and community relations and connectivity.

It means pushing up those programs of greatest importance, not just a little, but to high peaks of performance, while letting go of those things that just diffuse our focus on excellence.

It means getting buildings built, and to do it now.

There have been discussions about new and better buildings in the organization for the entire 22 years I have been here. None have appeared. Without such, keeping the level of excellence we have achieved as a collective is unlikely.

Personally, success means spending more time golfing with my wife, Janet. It means doing the same with my grandson, Oscar. It means having my own golf game continue to improve, despite my decrepit body.

I want to laugh out loud more than once or twice a day. Beyond games and sports, laughter is the heart of health!

QUICK FIRE QUESTIONS

Guilty pleasure? Too many to mention!

Favourite song to listen to (while looking for biomarkers)? Actually, I have a never-ending medley. Tends to be classic rock and ballads like “American Pie,” “Go Your Own Way,” “You’re So Vain,” “House of the Rising Sun,” “Heard It through the Grapevine,” “Man on the Moon.” Should I go on?

Luongo or Miller? Both excellent net minders and ultimately belong in the Hockey Hall of Fame. It used to be that Roberto [Luongo] could be dazzling and steal games, but I think he’s past prime for sure. Ryan [Miller] has cat-like quickness and a smoothness to his reflexes that is in a class above many. He still steals games. If the defence in front of him was stronger, the Canucks could win many more games, even without more offense.

Dr. Bruce McManus will be speaking at the upcoming Heart + Lung Health FEST Scientific Symposium, March 26-27. This year’s symposium features a session on biomarker research and the potential impact to clinical medicine, as well as a special session on science and innovation in BC. See the full program at fest.heartandlung.ca.