 Good morning, everyone. So my name is Pierre Moulien, I'm President and CEO of Genome Canada. I'd like to thank Jeff and Eric for inviting us to give a little bit of information on what we're doing in Canada regarding the implementation of personalized medicine, personalized health. I'd just like to acknowledge that we do everything in personalized health with colleagues from the Canadian Institutes of Health Research, and Paul Lasko is here this morning. And also my colleague Cindy Bell is also from Genome Canada in the audience. So what I'd like to do today is to give you a very quick introduction to the Canadian healthcare environment, because this is the receptor into which we're going to translate stuff. And I think it's very important that we understand what that receptor is like, what its culture is in order for us to do that. Then I'll tell you a little bit about genomics in Canada, and then go right into the meat of the presentation, which will be on a program that we have designed with our colleagues from CIHR in Genomics and Personalized Health, which we launched in 2012, and then a few conclusions and looking forward. So in terms of the Canadian environment, it's a publicly funded healthcare system. It's provincially delivered through a series of regional health authorities. So the regional health authorities are the payers of the systems, and they decide to a great deal what gets funded and what doesn't get funded in terms of technologies and so on and so forth. It costs the country around $200 billion per year. Growth is currently around the 3% annually, and given the general economic growth, this is not sustainable. But we know that biomedical research is very strong in Canada. In fact, we spend roughly 2% of global research, but produce 4% of the highest impact factor publications. And we also have very strong clinical networks, a lot of those were funded through the CIHR body, and for some diseases has among the best outcomes in the world through those networks. But the challenges are really our ability to move the latest technology into the healthcare system, which we do not have a very good track record of doing. And new technologies are often seen from the payer standpoint as just an added cost. And economic analyses performed are not obviously convincing enough for the payer to adjust their offer. So in terms of genomics, and we've benefited, I guess, from a sustained, focused investment from the government over the last 13 years. We were kind of playing catch-up to a little bit of a degree. And we're organized, we look like the federal provincial government, because we organized Genome Canada and six administrative regional genome centers, and their job is really to monitor large-scale projects and fundraise for us through looking for provincial dollars and other dollars that we can match federal dollars with. We also have five science and technology innovation centers, and they're the big, either DNA sequencing centers or proteomics or metabolomics, and I'll be talking a little bit about those and their role in some of these projects. And we've invested about $2 billion. One billion has come from the federal government over the last decade and a bit, and one billion then from other sources, including the provinces. I'll just talk a little bit about some of the challenges with translating new technologies, because obviously we're not going to translate something that has not been clinically validated and something like DNA sequencing, where there are multiple platforms, where the technology is probably, some platforms are more stable than others, and there will be new platforms coming forward as we go forward, because the technology is moving so fast. So that decision point as to when to transfer is going to be a key one. And then we have to ask the questions, well, once again, the receptor in terms of the clinical laboratory structures, are they going to be turned upside down, and what are the implications for that? And who will be making these decisions, and based on what criteria in terms of technology assessment, based on sound economics and clinical benefit, and who will pay for this stuff? So we decided then, talking with our colleagues at CIHR, that what we needed in Canada was some kind of demonstration that, one, the technology can deliver real value to patients, and two, integrating this technology within the healthcare system would be cost effective. And so we decided that we would design a program, and this is where we're hoping for some value add from a funder perspective, in terms of we had to make sure that the right team is going to be formed to do this translation, that the right deliverables are achieved, and that we have, we ensure true demonstrations of value that are obtained, and obviously that is then linked with how you organize, not only design the RFA, but organize the review panel, which was very, very critical. So in 2012, then we came together with our colleagues at CIHR and designed a new program. This was a major partnership between the two organizations. We pooled together $65 million of our monies, and we were able to leverage that up to $150 million through partnerships. And it was very interesting that obviously having a Genome Canada CIHR partnership in this area was a focal point for others who were interested in personalized health, and we were able to attract other investments into this pool. So going from $65 to $150 was, I think, a good, it obviously demonstrated that we could attract others and that others were very interested in joining us in our efforts here. So I'm going to just skip over this one and tell you a little bit about the key features of this competition. We insisted that the project teams come with a rationale and an economic analysis for why the particular application that they were proposing would add value to the healthcare system. We insisted that the assembling of the team and who those people were, including end users, health authority personnel, who would actually be the pool mechanism for some of these technologies. And a detailed development plan was required to demonstrate the integration into the healthcare system, including engagement by end users, considerations of the regulatory framework existing in Canada, and then looking at challenges and barriers to translation that we put under the GELS acronym, and I'll tell you I have a specific slide on that. So GELS are the genomics and its ethical, environmental, economic, legal, and social aspects. I think you have similar programs in your own countries, probably called a little bit differently. And this traditionally in genome Canada language has been related research undertaken from the perspective of the social sciences and humanities disciplines. In the context of this RFA, it was extended to cover researchers in the fields of health administration, health management, health services research, health technology assessment, evaluation, and comparative effectiveness studies. And those were integrated into the project in a mandatory way. There also was a possibility of a standalone project which would only deal with GELS aspects of this technology. And we're also going to bring the successful applicants together early next year, or early this year rather, to talk about do a bit of cross-fertilization and testing to see if there are common themes, common barriers, common issues of translation that we could fund some further GELS type activities in this domain. So the review was in two phases. We had 146 pre-applications that were reviewed by a very large group of people. And full proposals, that was whittled down to 40 full proposals. And they were reviewed by 40 international translational researchers, social scientists, and health economists. The panel chair was Raju Kushalapatti from Harvard Medical School. And I know that some of you are also involved in the process. Jeff was involved in the process. And Howard McLeod was involved in the process. And others may have been that I am not recognizing. But that review of full proposals took place over three days with face-to-face meetings between members of the review panel and project team applicants. And the review criteria were obviously research merit, but also very importantly, socioeconomic benefits, finance, and management. And those review criteria were reviewed equally. So it wasn't as if we were saying, well, yeah, the research merit is more important than the socioeconomic benefit. No, you could fail a project on any of the criteria. And we ended up funding 17 projects that are now have been all launched, and with an average dollar size of 8.8 million. So there are some that are 12 million. There are some that are 6 million. But that's the average size. And we traditionally in genome Canada have always been milestone-driven in terms of how we manage our projects that are closely monitored by personnel at the genome centers. We've introduced with our partners a new type of oversight committee as well for this competition. And that oversight committee, the ROC, reports to the funders on progress, provides advice to the project teams and helps ensure teams focus on reaching project milestones and objectives. So I'm just, I think I have a few minutes to 40 exactly to tell you a little bit about some of the projects. First of all, we were pleasantly surprised at the broad scope of the disease areas that were funded. We thought, at the beginning, is it just going to be cancer and pharmacogenomics? But no, it's across epilepsy autism where you can read them there. I'm not going to go through them. They do have a common theme, however, and it's to do with and that's not surprising in molecular medicine, molecular stratification of patient populations to inform decision-making re-effectiveness of drugs, adverse drug reactions, intervention strategies, and disease management. And they all have an economic rationale behind that. So for example, the first one on the list is epilepsy and a third of the epilepsy patients that come in do terribly on traditional anti-epileptic drugs. So you don't want to put those people on traditional anti-epileptic drugs and so the project is to do with getting a new diagnostic test together to differentiate those populations that will do well and not. I thought I'd just give you a flavor of the type of project. So this one is in lymphoid cancer run by Joseph Connors at the British Columbia Cancer Agency with link to, of course, the high-end sequencing center there directed by Marco Marra. And in this one, the beauty of this project was that Joe had gone around the province of British Columbia and had signed on every single clinical oncologist specialized in hematological cancers and brought them into the team and got them to sign on to say that, you know, yes, if this works, then we will apply it to my cohort of patients, et cetera, et cetera. So that's a very interesting one. There's also one on prenatal aneuploidy screening and this is looking at direct comparison with several technologies head-to-head and obviously you can imagine some of the gels-related research that's going on in that project. Everybody has their favorite story on rare disease. This one, these guys have gone through the usual diagnostic odyssey and for over a decade and of course three weeks after their genome sequence, their disease was solved. Now Kim Boycott and her group have solved over 150 cases out of 250 families that have been looked at. So that's a 60% hit rate. I'm not going to go through this because I'm now running out of time and I'll just go through some of the conclusions and the future aspects. So obviously we need to look, concentrate on the receptor and we're hoping that some of these project that we're funding will deal with some of these issues. Involvement of the private sector is key. There are 20 companies that are involved in the portfolio of the 17 projects that we're funding. So there is quite a lot of industrial interaction and you can read those, the other things on the list are obviously very similar to what you've already heard from the others. We have created in Canada and this is a unique thing in Canada for the moment. It's one of the first pediatric clinical genomic centers in the world. It's a partnership between Sanctus Dean University Hospital and Genome Quebec and will be a very interesting one to follow as a model for the system. So as Francis Collins always says, this is the beginning of something and not the end of something. The knowledge base will be totally different in five years once again and we'll be layering proteomics, epigenomics, microbiome data on top of our personal genome sequence which is going to have huge informatic challenges that Dan told us about earlier on. But it will mean that in ten years technology will allow us to do things that are totally unimaginable today. So I'd just like to acknowledge the genome centers which is very much of a family in Canada in terms of the genomic center prize that we created and of course our partners, it has been a superb partnership with CIHR and of course all my colleagues at Genome Canada for all of their help in putting this together. Thanks very much for your attention. I think I have a couple of minutes for questions if there are any. This is a question that I have because I've sort of been involved in the Genome Quebec post-award evaluation. You invested a huge, or you are investing a huge amount of money in 17 different projects. Is there some kind of plan to create a common infrastructure in terms of a genomic database or exchange of information or lessons learned across these 17 individual projects? There's a big investment in the individual projects. How about the collective? How are you approaching that? Terrific question Dan, thank you. And I mentioned that we were going to bring these 17 together once they were launched. We're going to bring these 17 together in April of this year and we're going to ask them exactly that question. What can we do to try and harmonize what you're doing to integrate data sets to make sure that we're harmonizing as much as we can do across these 17 different projects that are scattered across the country. And there is a link here between Canada getting prepared to be a credible partner in the Global Alliance and being able to integrate some of this stuff across the 17 projects. So it's a great question and I'll be able to tell you more after the April meeting then, so thanks.