In 2016, four BC Cancer Agency scientists were recognized as having peer reviewed papers that rank in the top one per cent by citations from publications in their field. They include Drs. Marco Marra, Steven Jones, Joseph Connors and, recently retired, Randy Gascoyne.
Marco Marra and Steven Jones, Distinguished Scientists at the BC Cancer Agency and Co-Directors of the Michael Smith Genome Sciences Centre, discuss this significant achievement.
Marco Marra (MM): Science isn’t something that’s done in which some lonely soul dresses in a lab coat and hovers under a naked lightbulb until the wee hours and that’s where it begins and that’s where it ends. Science is an intensely social activity actually, that in order to be effective has to be appreciated and absorbed by many folk all around the world. So, I guess what this means to me is that some of the stuff that we are producing, our scientific product if you like, is of interest around the world. So, I think we’re achieving our mission as scientists.
Steven Jones (SJ): What they mean by influential is that people are actually taking notice of the work that we’re doing and applying it to their own scientific research as well. So it’s fantastically important that the work that we’re doing has impact around the world and that what everyone has done here people are taking notice of.
MM: The focus of the work that we conduct at the Genome Sciences Centre (GSC) relates to trying to understand how information encoded in the genome – all of the DNA of individual cells – is interpreted by cellular machinery to encode biology. And to understand, when there are errors in the genetic code, how those errors can influence disease processes, how they can cause disease and how they might offer insights into how to better treat disease, in particular cancer.
SJ: Analyzing tumour DNA requires a huge amount of computation. If someone were to walk around the BC Cancer Agency’s Cancer Research Centre, they would see a lot of very traditional lab space. What they may not realize, because it’s kind of hidden away, is that we have one of Canada’s largest computers setup essentially just to study cancer DNA. That computer is running 24-7 and conceivably that’s not enough. We need more computation. And that’s because the genome actually has a lot of information in it. Analyzing this information involves great banks of computers to really understand what cancer mutations mean and what drugs a tumour may be susceptible to.
MM: A while ago, the GSC celebrated a milestone achievement: we sequenced a petabase of DNA. A peta is a one followed by 15 zeros. This petabase represents an enormous quantity of information. In fact, if you were to print out, in six point font, on 8 ½ by 11 pieces of paper, on both sides, no margins, a petabase of DNA sequence, you would have a stack of paper 1,700 km tall. So resident within all that information are clues about how the biology of cancers matter, how they evolve, how it might respond to certain treatments. Fundamental properties of the cancer are revealed if one can find the nuggets of information in this sea of background data.
MM: We’re probably not going to cure cancer in the way that we think about curing cancer. It is not actually “cancer”, it is “cancers” — and there are 200 odd diseases that we lump into “cancer”, and their biology is very different. So, what we will do is chip away at the individual biology of those diseases and we will understand them and we will come up with solutions. The past tells me that this is so, I believe it and that’s why I do it.
SJ: We are making huge strides in terms of our understanding of how cancers work. We’re making huge strides into understanding how cancers differ between people, even though ostensibly they may appear to have the same cancer. The question we really want to ask, because there must be an answer to this, is: why do some people respond to treatment and why do some people not respond? And that’s really the first of the research that we’re trying to do here, is to try to understand the responses and the non-responders, and could the non-responders be responsive to a different therapy.
MM: Precision medicine, in many respects, has arrived. What we mean when we use that term, is that we’re going to take a great deal of intensive measurements from tumour DNA and normal DNA from an individual patient, and from that information we are going to look for clues as to what’s driving their cancer in order to find a specific treatment to attack that specific cancer. We’ve already helped bring precision medicine to the clinic now by looking at a small number of genes arranged into assays that we called “panels” that focus on certain disease types. However, the vision would be that at some point in the future we will be able to capture all the information from all the genes involved in creating cancers.
And this brings us to a very important point: we can have all of the technology in the world at our disposal, unless we have a whole bunch of other collaborative opportunities we can’t really use this information the way we want to. We absolutely have to be working with a bunch of people in the clinical realm. And that is one of the huge strengths of the BC Cancer Agency: it provides the environment to actually think like this. But if you appreciate that we have 25,000 new cancer diagnoses in the province every year, of which 10,000 will be metastatic cancer, we have an amazing obligation to do even better.
SJ: I think one of the exciting things will be not to act just as a single hospital but to come up with ways that we can share similar data with other hospitals, conceivably across Canada, then maybe North America and then maybe the entire world. I think that will give us tremendous power. I think if all the hospitals that are doing this kind of research are actually sharing data that would provide this kind of research with much more power than you would ever have as just a single research centre.
MM: The BC Cancer Agency can absolutely make world-leading contributions here. We’ve shown that already. But we’ve just scratched the surface. Going forward, we can’t do any of this without the patients that participate in the research. So we need the support of the patients and their families, to engage with us, and we need the partnership of the clinicians that are treating these patients. Although the things we discover here are interesting in an academic sense, unless they can be tested in patients we really haven’t learned much about the impact on cancer. So the real challenge is for us to organize into a single force with a mission to understand these very fatal cancers and come up with solutions. That’s a tall order. It goes far beyond the lab, but it’s one that we must embrace.