| This article was originally published by Neuron, Volume 95, Issue 5, on 30 August 2017, Pages 1002-1006. |
Why Are We Doing This?
Diseases of the brain are one of the most compelling unmet medical needs of our time. The World Health Organization estimates that one billion people are affected by neurological disorders and that 6.8 million die every year from these illnesses (World Health Organization, 2006). As our population ages, these numbers are rising dramatically, placing additional burdens on health services and causing untold human suffering in developed and developing nations around the world. Contrary to cancer and heart disease where remarkable advances have been made over the last decades, we still have no disease-modifying treatments for debilitating neurological diseases such as Alzheimer’s, amyotrophic lateral sclerosis, autism, and Parkinson’s.
While neuroscience is thriving, our understanding and management of mental and brain disorders has changed little over the last few decades. Neuroscientists are working to understand the basic biological mechanisms of neurological diseases, yet with billions of neurons and trillions of connections, a complex anatomy, and limited access to tissue, we are still at the dawn of understanding the workings of our brain. Without a more complete knowledge of the brain and its diseases, the development of targeted treatments remains slow and is frequently empiric. The pace of progress is too slow for those afflicted with a disease of the brain. Hence, there is an urgency and an ethical obligation to act now if we are to find the cures that will reduce the burden of neurological illnesses for the next generation. To speed up the process of discovery, we need to better share data and reagents, and avoid duplication or triplication of efforts, by allowing the free flow of information.
Openness and collaboration form the cornerstones of a new initiative at The Neuro (Montreal Neurological Institute-Hospital), the Tanenbaum Open Science Institute (TOSI), with the objective to expand the impact of brain research and accelerate the discovery of novel therapies for patients suffering from neurological diseases.
Our position is that research is not an end in itself, but rather a way to fulfill our ultimate mission: delivering discoveries for the benefit of patients and their families, while making the best use of public resources. With that perspective, Open Science (OS) is an attractive and promising new way of doing research to spur innovation and accelerate knowledge discovery and exchange.
As defined by Nielsen (Nielsen, 2011), “Open Science is the idea that scientific knowledge of all kinds should be openly shared as early as is practical in the discovery process.” Historically, it has been associated with open sharing of scientific publications and research data but has now broadened to open sharing of tools and materials (ranging from codes to human samples), the absence of intellectual property (IP) protection, and open commercialization in specific circumstances. At The Neuro, we see OS as a means to expand the impact of our research through a global community of like-minded scientists and we embrace all of the elements of OS stated above.
OS, with sharing of large-scale data and reagents, has been enabled by the rise of the internet and the emergence of powerful data sharing tools. In addition, the computer age and the internet have created a new mindset for the conduct of research. From the free software movement led by Dr. Stallman, to the Atlas experiment in particle physics, or the Human Genome Project in the biomedical field, several successful and impactful OS initiatives have been conducted over the years. In the Human Genome Project, formal agreements were made to encourage free distribution of research data, a ground-breaking event for biomedical research. Before the project, scientists had typically shared their research findings in scientific journals. By the end of the project, scientists were willingly sharing their findings with each other, as well as the public, long before publication, which was key to the success of the initiative and contributed to the exponential outcomes that we all know today (Tripp and Grueber, 2011).
Who We Are and How We Did It
The Neuro offers the ideal environment for a novel and comprehensive OS initiative. Its mission is oriented on a patient-focused research continuum from the patient’s bedside to the scientist’s lab bench, and back. The institute is configured to encourage clinicians and researchers to meet and collaborate. All clinical and research activities and facilities are housed under one roof. Its current director is a leader in OS and conveys this philosophy not only as a researcher, but also as a clinician. Together these elements provided a strong foundation that facilitated embarking on a journey to become the first OS Institute in the world and adopt OS as a core value of The Neuro. To fulfill that aim, we decided to create the Tanenbaum Open Science Institute (TOSI), which was officially launched on December 2016. TOSI has the mission to develop OS Policy and to implement OS Principles for The Neuro and its OS partners.
An important element in the successful creation of the TOSI was the 18 month buy-in process involving all faculty, research staff, students, and administrators that we did before announcing its launch. We started by a due diligence exercise on existing OS activities versus closed activities at The Neuro, to confirm that many ongoing research activities were already operating either fully or partially in the open sphere. After a series of lectures on relevant OS initiatives such as the Structural Genomics Consortium or the Sage bionetworks and their respective impact, we embarked in a consultation process with Neuro faculty, staff, and students through polls, town halls, retreats, and Q and A sessions. This consultation process resulted in a definition of OS that would serve the mission of The Neuro, including to which point research activities were suitable for OS and when they could be developed as in the proprietary sphere (for example, sponsored clinical trials are not part of OS at The Neuro). The consultation process also helped to define the infrastructure and platforms that would be included in TOSI and further developed by The Neuro to support our research community in conducting OS research. As an example, a recurring concern was the additional workload that researchers would have to face by granting access to their research data. We made the commitment to our research community that this additional burden would not be placed on them but on a team of experts supported at the institutional level that would facilitate the implementation of open access to data from design of appropriate software packages to data entry and data curation. We also collaborated with Dr. Richard Gold, (Associate Dean and professor at the Faculty of Law at McGill, and founding Director of the Centre for Intellectual Property Policy), to conduct a social science study on potential barriers and limitations related to adopting an OS policy. In the context of this social science study, confidential structured interviews were conducted with a diverse range of Neuro researchers with the objective to explore their experience, opinions, and concerns regarding OS. A report on the research findings was broadly distributed to The Neuro research community and served as a basis for the establishment of the five guiding principles for The Neuro's OS policy (Figure 1).
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Figure 1. TOSI Guiding Principles
The entire Neuro research community agreed to adopt these guiding principles during our annual retreat. We also had the enthusiastic support of Pr. Suzanne Fortier, Principal and Vice-Chancellor of McGill University, and of the senior leadership of the University. This support was instrumental to the OS initiative and resulted in constructive discussion on how to integrate this initiative in the broader context of McGill University, as well as to have the initiative recognized as a pilot for the entire University.
What Do We Aim At?
OS is a global movement, with followers in Canada, the United States, Japan, and the European Union, among others. The European Union and Japan have both implemented national programs supporting OS. The UK Wellcome Trust, the U.S. National Institutes of Health (NIH), and the American Howard Hughes Medical Institute recently launched an OS Prize to unleash the power of open content and data to advance biomedical research and its application for health benefit. Other research organizations such as the Allen Brain Institute, the Structural Genomics Consortium, and the SAGE bionetwork have also embraced the OS philosophy.
OS at The Neuro is designed to accelerate discovery, innovation, and research impact by encouraging rapid, collaborative, and public sharing of data, samples, scientific tools, as well as OS policies. TOSI is implementing OS principles at The Neuro along five spheres of activity supported by structural pillars (Figure 2):
- Open Access, by creating an MNI Open Publishing Portal with international OS publishing partners to publish research results, including negative results, without restriction.
- Open Data, by sharing experimental data freely and meaningfully with institutions around the world using a robust cyberinfrastructure platform.
- Open IP, by refraining from pursuing patents on Neuro-generated discoveries at large and developing new collaborative models with industry through our Open Drug Discovery Platform.
- Open sharing of biological samples and other resources collected through The Neuro's Clinical Biological Imaging and Genetic Repository (C-BIG Repository), within the limits of supply and respecting patient confidentiality.
- Open Commercialization, by developing new business models and initiatives to bring open science discoveries to the marketplace, including new medicines.
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Figure 2. TOSI Major Pillars
As the first leading academic research institution to develop an OS framework at the institutional level, a robust cyberinfrastructure platform plays a critical role to allow sharing of data and materials. Several key implementation hurdles have to be addressed concerning policy, security and ethical issues, infrastructural design, data harmonization, processing, and software interoperability. For effective data sharing at an institutional level, it is imperative to use a robust cyberinfrastructure capable of incorporating multiple studies from various principal investigators (PIs), as well as integrating workflows and interoperability with platforms that capture and disseminate large datasets. Such a solution must also support open access to a wide array of data modalities collected across the institute within a single platform, including clinical and behavioral measures, biological samples from The Neuro C-BIG Repository collections, genomic data, and a growing multimodal repository of brain imaging data. The neuro-informatics infrastructure (CBrain and LORIS) developed over the years by Dr. Evans at The Neuro is addressing these challenges and will provide the necessary informatics infrastructure, which will be made freely available to other institutions to facilitate their adopting an OS policy.
Beyond cyberinfrastructure, TOSI relies on other pillars such as the Open C-BIGR and the Open Drug Discovery Platform (ODDP). The C-BIGR is a source of information linked to biomedical specimens that will be freely shared. It is designed to become one of world’s largest libraries of combined brain imaging, clinical, demographic, genetic (DNA), and cell data, with biological samples from patients, all with neurological disorders. It follows the emerging social innovation in research and healthcare model whereby patients actively participate in their own care, and continuously enrich and expand its content, while protecting patient privacy. C-BIGR is based on the strategy whereby we obtain deep phenotypic information about each patient as well as a variety of bio-samples. The Open Drug Discovery Platform joins the efforts and complementary expertise of several initiatives that include the Brain Canada iPSCell/CRISPR platform, the Neuro-SGC platform (assay development), and the Neuro-CDRD (Center for Drug Research and Development) platform (automation and screening). These combined platforms make use of iPSCs derived from C-BIGR samples to create disease-relevant assays in deeply phenotyped patients that should facilitate accurate therapeutic target identification, all to bring new drugs more rapidly to market. This is a unique pan-Canadian public-private partnership jointly managed by The NeuroI, the Structural Genomics Consortium (SGC, Toronto), and the Centre for Drug Research and Development (CDRD, Vancouver) with the financial and scientific support of the pharmaceutical company Merck, ALS Canada, Brain Canada, CQDM, SGC, and philanthropic partners. Access to the novel high-quality tools generated by these platforms (structures, gene expression and silencing, proteins, antibodies, molecular probes) in a variety of patient-specific neurons should help scientists, industry, and patients because it will facilitate the elucidation of disease mechanisms and the discovery of novel therapies in the cell types most relevant to the disease.
Contrary to most OS initiatives, TOSI does not restrict itself to developing a research infrastructure that enables data sharing. It is also developing a broad array of programs, partnerships, and research policies to promote and facilitate adhesion to OS principles. To name a few, we are defining (1) appropriate incentives for researchers to adhere to OS principles, (2) new OS policies with Canadian (Open Government) and international governments (EU), (3) new models for commercialization in the open space, as well as (4) new collaborative models to support innovation with Canadian and international partners. The Neuro's OS Initiative is a novel social science experiment in how we collectively govern, conduct research, and develop innovation in the open. We have a responsibility to our patients, our researchers, and our financial backers to demonstrate that the initiative will fulfill its promises. Our expected outcome is to have a significant impact on the pace of discovery. For example, The Neuro has taken the position not only to openly share but also to not file for patents on any of its discoveries, and to encourage our collaborators and industry partners to do the same on shared discoveries. We think that there is a real benefit for industry to enter into open collaborations, skipping costly negotiations over intellectual property rights and royalties, and increasing innovation by reducing transaction time and cost, and by facilitating the entry of non-traditional firms into the mix. In addition to speeding up innovation by eliminating time spent negotiating IP rights for early-stage discoveries, we hope OS will also allow patients and research study subjects to more actively participate in research and allow healthcare providers and hospitals to more quickly put clinical innovations into practice and to introduce medical discoveries on an accelerated pace.
Given the experimental nature of our initiative, which is first and foremost a social experiment, we have fostered the creation of an Evaluation Committee to independently measure, compare, and assess the performance of TOSI and associated projects. The Neuro will collect data about OS’s concrete effects on research, collaboration, uptake by other institutions, the local economy, etc. The Evaluation Committee will test these hypotheses by monitoring us for the key expected outcomes of our OS initiative. By measuring the impact of our efforts, we hope to validate the OS approach and push this movement forward. It will allow us to convincingly advocate for OS and help other institutions that think it is a good idea to make the leap to OS. The work of the Evaluation committee will also determine whether and in which contexts openness is a more effective research and innovation strategy than are other models; measure results and encourage deeper understandings of the process by which we create, share, and use knowledge; and develop international standard measures so that institutions and governments can assess different models of innovation.
Update after One Year
During the past year, we focused our efforts on structuring the initiative, establishing its governance and internal implementation committees, obtaining funding through grants and fund-raising, coordinating aligned and harmonious development of the various pillars, and on propelling the cause of OS by responding to the interests of numerous national and international parties interested in joining or at least knowing more about the movement.
On the governance aspect, TOSI now has a Leaders Council, composed of distinguished leaders from a cross section of business, professional, and community sectors across Canada and internationally, with a track record of preeminent leadership in their field and extensive experience operating in a transformative environment. Dr. Heather Munroe-Blum (Chairperson, Canada Pension Plan Investment Board [CPPIB] and Emerita Principal [President], McGill University), Mr. Larry Tanenbaum (Chairman and CEO, Kilmer Van Nostrand), and Dr. Guy Rouleau (Director, The Neuro) are ex officio members of this Committee as Founders of TOSI. This high-profile committee’s mandate consists in brokering, fostering, and nurturing relationships to guide The Neuro’s transformative journey to become the first OS institute in the world, and in promoting, supporting, and propelling the cause of OS to accelerate discovery and enhance the consolidation of a robust framework for strategic partnerships in OS.
We also established internal committees and working groups. The Platforms Leaders Group ensures an aligned and cohesive development and implementation of all platforms supporting TOSI’s vision and mission. The C-BIGR Committee coordinates the development of the C-BIGR in full alignment with key Neuro units and in full respect of Research Ethics Board’s recommendations. The Tissue and Data Access Committee ensures that data and samples collected in the C-BIGR are made available to research teams with scientifically and ethically valid proposals around the world. A working group has been established to address issues of data sharing across multiple jurisdictions. Additional committees might be created as the need arises.
Ethics approval has been obtained for data and bio-banking for patients with neurological disease and healthy controls, and the C-BIGR is actively recruiting data and materials from patient’s with Parkinson’s disease, amyotrophic lateral sclerosis (ALS), neuromuscular diseases, and brain tumors.
In-depth definition of features and requirements of The Neuro institutional Open Access and Open Data portals are being finalized, including a user-experience approach, and benchmarking various platforms and tools that would fit these requirements, complementing our existing IT infrastructure. This includes an advanced data management system, LORIS, and a high-performance computing platform, CBRAIN.
With close collaboration with partners like SGC (Structural Genomics Consortium) and CDRD (Centre for Drug Research and Development), the ODDP has implemented disease-relevant cell-based assays using neurons differentiated from patient-derived iPSCs and initiated partnerships with pharmaceutical companies for drug screening in the Open pre-competitive space. These initial collaborations will help sharpen the business model of open drug discovery, which is a work in progress.
The Evaluation Committee has been successful in engaging high-profile stakeholders and partners to both fund and participate in the different workshops that will allow the identification of big questions related to OS and metrics for future measurement of impact. First of these series of workshop will take place this October in Washington, DC, and include stakeholders like Wellcome Trust and Gates Foundation.
TOSI is also working on building an Incentive Fund to incentivize other institutions and researchers all across Canada to embark on OS policy.
Developing an OS framework is costly and there is for now no obvious source of funding, either from government or funding agencies. As an example, supporting OS at The Neuro requires an institutional investment in scientific talent, space, and specialized equipment. This includes adapting our IT infrastructure to support sharing of multimodal data, and creating and growing C-BIG Repository and the Open Drug Discovery platform. Overall, we estimate the cost to develop and implement OS at The Neuro around $CAD 85M in total for the next 7 years. So far, we have obtained $CAD 42M in funding, including support from federal and provincial programs, industry, and philanthropy. It will be crucial for the success of OS that governments around the world develop not only OS policies but also devote some funds to support OS-specific needs.
We are also actively recruiting scientists who are OS advocates and who will contribute and shape the future of the OS initiative. Interestingly, we have noticed that all the young potential new recruits to The Neuro are actually very keen to work in an OS research environment and that OS acts as a magnet for recruitment, rather than as a threat. Contrary to what some might think, OS is not perceived as a risk in their careers, a testament to the younger generation that bodes well for the future. It will also be important for our institution to ensure that we build appropriate mechanisms to measure and recognize the contribution of our scientists in the OS field.
Lessons to Share
This first year into the OS journey has shown us that creation of TOSI was possible due to the existence of key ingredients: a robust boat (Neuro infrastructure), a captain, and a willing crew (Neuro scientific community, its patients, and McGill University), all ready to embark on the journey.
We were fortunate that as part of The Neuro past, we had developed a number of key resources, such as a state-of-the-art infrastructure to support our multimodal brain imaging center and an ethics framework. These assets took years to build. This is facilitating our tasks, which include the deployment of the OS cyberinfrastructure, as well as technological platforms such as C-BIG Repository, the ODDP drug discovery platform, data sharing tools, and a strong legal and ethical framework for sharing patient material and patient information. We strongly recommend to others who want to develop an OS framework to build, as we did, on existing assets and strengths, and to tailor their OS definition to what will best serve the unique mission of their institution.
Another important lesson would be to be patient and resilient. OS science is first and foremost a change in culture, and humans don’t like to change. A clear and consistent message, a bottom-up approach for consensus building, an education strategy, and a cautious and respectful approach to implementation will increase the likelihood of success. Nonetheless, each initiative will be constantly challenged and judged, and the answers or the solutions will not necessarily be immediately obvious. Also be daring, as embarking on a journey without knowing the exact destination is challenging, but nonetheless a great adventure. Finally, do not let complexity, skepticism, or specific operational barriers deviate from the ultimate goal. In our case, it is patient centric aimed at accelerating the discovery of disease modifying treatments.
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