Dr. Jim Russell: 30 years in critical care and severe infection

11 April 2017

Dr. Jim Russell is professor of medicine at UBC and researcher in the Centre for Heart Lung Innovation at St. Paul’s Hospital. He is an internationally recognized leader in the fields of critical care, severe infection and clinical trial design.

On April 19, Dr. Russell will be presented with the 2017 Aubrey J. Tingle Prize in recognition of his contribution to health research and the health system in BC and globally. Here, he reflects on 30 years in the fields of critical care and severe infection.

Firstly, congratulations! What was your first response when you heard you’d been awarded the 2017 Aubrey J. Tingle Prize?

I couldn’t believe it! It’s such an amazing recognition and validation of all the hard work you do, and incredible to get that recognition from peers and an institution that I respect hugely.

I was already a mid-career researcher when MSFHR was founded so I never received an award myself, but I’ve actually had the honour of meeting both Michael Smith and Aubrey J. Tingle. The vision to support young faculty in the early stages of establishing an academic career is so smart. It’s such a challenging time, but helping kick start these young researchers is a wonderful strategy and helps them compete at a national and international level, and improve our standing as a province.

You are being presented with the award in recognition of your work in critical care, sepsis and severe infection. What first drew you to these fields?

Sepsis is basically a severe infection. We’ve all had a cold or the flu, so imagine that but ten times worse. And then your organs start to fail, your heart, lungs, kidneys and eventually the brain.

What a lot of people don’t realise is sepsis kills more people than heart attacks. Even with antibiotic treatment a third of patients will die and there is not one single approved drug for sepsis anywhere in the world. It’s a devastating illness and it was probably in my second year of training in critical care research that I really decided I wanted to do something about it. Even now we don’t really know how sepsis causes organ failure, so that’s what we’re trying to figure out at the Centre for Heart Lung Innovation.

When you founded the Critical Care Department at UBC and St. Paul’s in 1982, did you have any idea it would grow into such a well renowned unit?

I remember coming from Toronto General Hospital to St. Paul’s for the ICU director interview and distinctly remember telling the chair of the search committee that I wanted to create the best critical care research group in the world. His response was ‘You must mean Canada?’. But no, my intention was always to make the unit at St. Paul’s world class.

At the time our approach was seen as quite revolutionary. Our team would spend 75% of their time on research and 25% on clinical work. It meant we had world class clinicians doing the research, taking care of the patients, and training the residents. When you have patients with multi-system organ failure and on an average of 14 IV medications you need that kind of expertise and the department grew quickly from a starting point of just one researcher with one grant and one research fellow.

Alongside your research and clinical work you’ve also found time to create two companies, Sirius Genomics Inc. and Cyon Therapeutics. What prompted you to make the jump from research to commercialization?

At the time I started Sirius I was extremely busy with clinical work, research and my role as the Chair of Medicine at St. Paul’s. But one Wednesday a 25 year old dad got a sore throat, went to see his GP and was prescribed penicillin. On Friday he arrived at St. Paul’s with septic shock and acute respiratory failure. We put him on life support and supportive care but by Saturday his kidneys failed, and by Sunday he had multiple cardiac arrests and died. It was devastating. He was a healthy young man and the same age as my elder daughter. It was at that point I thought ‘we have to do better’.

At the time my colleague Dr. Keith Walley and I had been making some exciting discoveries around genetic variation that seemed to indicate who would respond well to a new sepsis drug. We had the idea to create a genetic test that could predict who would respond well to certain drugs to help clinicians make more informed choices about what to prescribe (i.e. personalized medicine).

I wasn’t certain I wanted to go ahead with commercialization, but what swung it was the realization that if the test worked it could have far greater impact and save far more lives than me spending every day for the rest of my life in the ICU. So we created Sirius Genomics.

Fantastic! So what happened next?

We ran three studies, including a large international study with 10,000 patients, but sadly the third didn’t reach statistical significance. It’s a risk you take with projects like this but we certainly learned a lot from the experience.

Later I went on to co-found Cyon Therapeutics with Keith Walley, John Boyd and Simon Pimstone and used a similar approach but focusing on a drug rather than a test. We were the first in the world to discover that PCSK9 inhibitors, a type of drug already being used to lower cholesterol in cardiovascular disease, are effective in sepsis. In fact, people with a PCSK9 genetic defect have a 15% better chance of survival than those without the defect.

Now our goal is to develop a PCSK9 inhibitor that can be used alongside antibiotics to increase the chance of treatment success by using the body’s natural clearance mechanism to accelerate the excretion of the bacterial endotoxins that cause organ failure.

We’ve already licenced a potential drug from the pharmaceutical company Novartis. Pre-clinical and Phase I safety work is already done, so we should go straight into a Phase II trial by the end of 2018. Far faster than a normal small biotech.

Other than your ongoing work with Cyon, where do you see your research taking you next?

I think my next focus will be the long term consequences of sepsis – readmission to hospital, dementia, depression, etc. Things that aren’t very well studied at the moment.

I’m particularly interested in how we can reduce readmission (at the moment 35% of sepsis patients are readmitted within six months). In the longer term I’d like to see to see sepsis clinics across Canada so that discharged patients could go for tailored outpatient care to prevent longer term issues.

The Aubrey J. Tingle Prize is awarded annually to a British Columbia clinician scientist whose work in health research is internationally recognized and has had a significant impact on advancing research in his or her field — as well as the uptake of this evidence — to improve health and the health system in BC and globally.

The 2017 Aubrey J. Tingle Prize will be presented on April 19, 2017 at the 19th annual LifeSciences BC Awards.

Read moreDr. James Russell Wins 2017 Aubrey J. Tingle Prize