SickKids’ new Paediatrician-in-Chief weighs in on how far we’ve come and the power of integration in genetics

On July 1, Dr. Ronald (Ronni) Cohn stepped into his new role as Paediatrician-in-Chief at The Hospital for Sick Children (SickKids). As Cohn, Senior Scientist in Genetics & Genome Biology, prepares to lead SickKids into a genetics-fuelled future, he reflects on how the field has evolved, and looks ahead at the potential of individualized medicine in addressing currently untreatable paediatric conditions.

What made you decide to devote your career to the field of paediatric genetic medicine?

It’s interesting because I always thought I would be a surgeon – I wanted to be a trauma surgeon. I worked in the emergency room as a medical student. One of the first things I realized in the emergency room was that I was always particularly engaged when we had children come in. I started to figure out that this is the population of patients I wanted to take care of one day.

Then our very close friends had a child born with a genetic disease – diagnosed as a mitochondrial disease. I decided I wanted to write my thesis about this. And I did, but I didn’t end up becoming a mitochondrial expert. I did a clinical study and then decided I wanted to do basic science. So then I went on to do muscular dystrophy work. So that’s how I ended up in the neuromuscular/neurogenetics world, through a very personal experience.

What were the major clinical and scientific challenges in the field when you began your career, and what are the challenges today?

When I started medical school it was just about the time people started to clone genes. There was the identification of the cystic fibrosis gene and the Duchenne muscular dystrophy gene – we were just trying to do positional cloning for genes back then. With that, we could start to think about the underlying pathogenesis. We are still doing a lot of this, trying to understand why a certain gene mutation develops into a certain disease.

Once the dystrophin gene was identified as the cause for Duchenne muscular dystrophy, all of a sudden we started to develop a concept of what this disease is.

Since then, some major things happened:

First of all, as we gain a better understanding of the number of genes in a human genome, hundreds and hundreds of studies into different models of disease have been conducted and we are starting to understand more, find more and more genes, and learn how to better organize and share the genomic data to enable enhanced scientific and clinical discoveries.

But really the major change during my career has been the coding of the human genome, which is now leading to genome sequencing. We’re already utilizing genome sequencing frequently in the clinic. This has almost become a routine genetic diagnostic test – it’s not quite there yet but we’re going to get there soon.

And the next big thing that happened just three years ago was the characterization of this gene editing technology, CRISPR, which now gets us to a point where we can actually start to conceptualize how to fix a genetic disease. This is very exciting and challenging as a scientist and clinician.

When we started to identify genes for diseases – which is still an ongoing effort – it was just a handful of those that were known. There’s been rapid development in identifying genetic disorders and this will help us to ultimately achieve better patient outcomes.

Still, with the identification of these disorders, there’s not much impact when it comes to how you can manage or treat a patient. And now with this gene editing technology just at the cusp, I can actually start developing that concept of how could I actually fix this, which I couldn’t even be thinking about three years ago. It is amazing.

What achievement are you most proud of so far in your career?

That’s a hard question. If somebody asked me my proudest moment in research – I could answer that. That was when we were able to fix the muscle cells of a boy with DMD in the lab and the dystrophin came back. If you asked me what was the best moment I’ve ever had in research, then that was it.

But if you look at my entire career, at the end of the day, I’ve received a lot of feedback from parents who are just grateful for whatever we try to do to help them get through a difficult time.

And honestly, we all want to have a breakthrough research discovery, and maybe I foresee a bit of a eureka moment to fix a genetic disease in a child. But at the end of the day, there’s nothing more gratifying than knowing you just helped somebody get through a really, really tough situation.

What drew you to SickKids?

It really was the opportunity to lead a division in genetics which I thought had almost unprecedented opportunities, given the patient population we serve here and being an environment that can really move things forward.

When I interviewed here I made it very clear one of the goals was to make genetics not just visible within the hospital, but integrated into the hospital. And I imagined there was a terrific opportunity here. I think we have made significant progress.

One major contributor is the culture and dedication of the people who work here, from the physicians to the person who changes the lightbulbs. I feel like it’s close to unprecedented. That’s what makes this hospital such a great hospital – it’s because of the people who work here. Everyone in this institution rallies for our patients and is extremely proud to be part of that team contribution. And that’s what’s so special about SickKids.

Dr. Denis Daneman is leaving some big shoes to fill. How has he paved the way for you to bring SickKids’ Department of Paediatrics to the next level?

I’m not going to even attempt to fill his shoes, but what I’m going to attempt to do is to build on the legacy he is leaving behind. I think he is probably the best mentor I’ve ever had in my life, and I think that most of the people here would agree with me and say the same thing. He has this unbelievable mixture of intellect, sensitivity, humility – I’ve never met anybody like him. He’s a visionary guy. He sees what’s important in all different areas of paediatrics and he has made contributions and decisions that have put things into place that achieved great outcomes. I don’t have to come in and fix – I can come in and build, which is probably the biggest gift he is leaving behind, not just for me, but for the entire department.

How does being a clinician inform your science?

My clinic informs the questions I ask in science. When I see a patient, I bring it back to my lab for discussion. Everything in my laboratory is related to a patient’s disease. When students come to me and ask me about what I do, I tell them if you want to work with me, you need to know that I’m not doing the basics of basic science – I’m always asking a question that is at least somewhat related to a patient I see in the clinic.

How does being a scientist inform your role as a physician?

Wearing the lens of a scientist makes me a more critical thinker about my patients. I feel like it helps me sometimes understand why certain things are happening in patients because I have a bit of a different view in thinking about clinical issues. I’m not sure it’s better – it’s just a different approach to patients that is clearly informed through the science.

What’s on the horizon?

Where the power is going to be over the next 10 years is to finally integrate all the kinds of information we can gather from one patient. We’ve already started to do this: in sequencing the genome, you’re collecting an enormous amount of physiology data, environmental data and social determinants of health. By taking the individual and putting all the data we can get together, we’ll be able to understand the individual and treat the individual in a way that is really beneficial, and not just a “best guess” type of management and treatment but rather individualized patient care.

The transformational change is to combine all of this. And that’s what we’re going to have to do. Putting all these pieces together is what’s going to really deliver on what I like to call individualized care. This approach to clinical care will change the future of paediatric medicine; improving outcomes for kids with very rare diseases just as much as for kids with very common diseases.

SickKids is well-positioned to advance the field of genetics because…

… it combines successful cutting-edge research with an unprecedented patient population that allows us to actually translate and bring the research discoveries into clinic.