Building a Scientific Community that is More than the Sum of its Parts
What We Learned from the Neurodegeneration Challenge Network Kickoff Meeting
Everyone is affected by neurodegenerative disease, whether as a patient, family member, care-giver or citizen. The numbers alone are staggering. Without losing sight of neurodegenerative diseases as a global challenge, in just the U.S.:
- More than 5 million people have Alzheimer’s disease (AD). Estimates for cost of care for Alzheimer’s patients is $277 billion, which does not include unpaid caregiving and loss of income.
- 1 million people are living with Parkinson’s disease (PD), with 60,000 Americans newly diagnosed every year.
- 20,000 people have Amyotrophic Lateral Sclerosis (ALS). This year alone, 6,000 people will learn they have ALS, a disease that is usually fatal within two to five years of diagnosis.
- 60,000 people have been diagnosed with Frontotemporal Dementia (FTD). FTD is often misdiagnosed, so this number likely underrepresents the number of people with the disease.
As harrowing as these numbers are, they do not tell the full story of the immense physical, emotional and financial toll that these diseases present to patients, their families, and care-givers. It’s also important to remember that AD, PD, ALS, and FTD are only a subset of a large class of degenerative disorders of the brain and nervous system — including conditions such as Huntington’s, multiple sclerosis, traumatic brain injury, ataxias, and other disorders — that impact millions more.
Neurodegenerative diseases have few effective treatments and no cures. In most cases, we still don’t fully understand what causes these diseases.
The Chan Zuckerberg Initiative recently launched the Neurodegeneration Challenge Network as an innovative, new approach to address the science and underlying biology of neurodegeneration, so that we can ultimately find better ways to treat these challenging disorders.
Our vision for the CZI Neurodegeneration Challenge Network is to create a community with the potential to be more than the sum of its parts. We seek to do this by:
- Bringing together interdisciplinary teams of biologists, computational scientists, engineers, and physicians with new ideas about how to solve these disorders;
- Empowering them with robust, reliable, shareable tools and platforms; and
- Seeding a culture that values and supports collaborative efforts.
Through two open funding calls — one focused on early career researchers (Ben Barres Early Career Acceleration Awards), and the other on small group interdisciplinary collaborations involving clinicians and basic scientists working together (Collaborative Science Awards) — we selected the first new group of investigators for the Challenge Network.
In late February 2019, we brought together this group together for an inaugural kickoff meeting with over 130 researchers and clinicians, including 17 recipients of the Ben Barres Early Career Acceleration awards and nine Collaborative Science teams, along with postdocs, students and staff scientists, representing 26 institutions. CZI program staff, computational biologists, and engineers rounded out the mix.
Many in the group had not met each other before, and a sizable proportion of the researchers were new to the neurodegeneration field. As CZI is a relatively new funder in this space, most arrived at the meeting with questions, curiosity, and for some, a healthy dose of skepticism about what CZI intends for this Challenge Network and how it would be different from the existing consortia and collaborative funding groups that are common in science.
Our goal for the first meeting of this new Network was to bring these researchers together in order to start to lay the foundation for this new community and what we hope to achieve together. We hope that over the course of the meeting and the week together a clearer view emerged of how this Network can move the needle on the challenge of neurodegenerative disease. Here, we’re excited to share some of what learned at the meeting and how we are thinking about the path forward.
1. Collaborations — like relationships — need to be nurtured and developed
Collaborations are the cross-pollinators of science, bringing together diverse expertise and stimulating new ideas, models, and ways of thinking about a problem. A primary goal for this meeting was to introduce this new group so they can learn about one another’s science and hopefully spark some collaborations. Students, postdocs, and staff scientists are an important part of the Network, and we invited each of the project teams to bring trainees and staff from their lab.
We structured the meeting program to allow a lot of time for interaction — both scientific and social. The program included short talks from each team to present their work, plus breakout discussion groups to bring researchers together around shared goals; and presentations, panel discussions, and demos to introduce CZI to our newest investigators.
Of course, truly impactful collaboration that is more than just transactional takes effort and time, and like any relationship, to build a truly collaborative community, these connections need to be nurtured and developed. The kickoff meeting was just the starting point. Slack channels and a website designed to help nurture this community in virtual space are a part of the toolbox we plan to use to keep the Network connected after everyone returns home. We plan to take advantage of online tools and forums to meet virtually, and to share programming to support and engage the Network investigators. Looking forward, we hope that some of the collaborative sparks lit at the meeting will take flame.
2. We must change how we think of neurodegenerative disorders
A central part of the scientific vision for the Challenge Network is to reframe how we think about neurodegenerative diseases, shifting away from regarding them as singular diseases to viewing them as a broad class of disorders with common biology and underlying mechanisms, as well as shared clinical features and perhaps, common treatment and prevention strategies.
This may seem like a radical shift for a field where these diseases are still studied, diagnosed, treated, and organized around in largely separate domains. Here, neurodegeneration can learn a lesson from the cancer field, which went through a similar reconceptualization to shift from an organ-centered view of cancers — lung cancer, breast cancer, liver cancer — to a more integrated view of cancer, with the underlying biology at the center that ultimately led to a new range of therapies for cancers broadly. Likewise, there is a need to shift our view of neurodegenerative diseases as exclusive diseases of the brain, nervous system, and neurons to diseases of the whole body and diverse systems and cell types that are impacted in many ways by other organ systems, physiology, and the environment, in ways that we don’t yet fully understand.
The new Challenge Network investigators and labs reflect this broader vision for neurodegeneration. At the meeting, they shared insights into their research plans, which cover a broad scope — from understanding how astrocytes and glial cells are involved in synapse loss during disease to addressing the influence of the immune system and metabolism on neurodegenerative disease. They are exploring new technologies to model neurodegenerative disease using human-derived stem cells and new 3D mixed cell models, as well as cutting-edge single cell, genomic and computational methods to identify novel signatures of disease that may cut across different disorders.
Their work looks to address fundamental questions across neurodegenerative diseases — for instance, why the same genetic mutation in one person may lead to ALS in one instance and FTD in another, and why certain brain regions are more vulnerable to disease pathology than others. The meeting brought together experimental scientists, physician scientists, engineers, and computational biologists to share diverse perspectives and expertise in the hopes that this Network will be able to more readily unlock novel solutions to these challenging questions.
3. It’s important to stay close to the work
At CZI, we often talk about the importance of “staying close to the work,” which means that as funders and technologists, we feel that it is critical to know and understand the needs of the people and communities we are trying to serve. Although the majority of the Challenge Network teams are focused on basic science and understanding the fundamental mechanisms that underlie neurodegenerative diseases, ultimately, we all want to solve these diseases.
To bring the perspective of what living with these diseases means to patients, a centerpiece of the program was three presentations that brought together a clinician and patient or patient’s family member to provide a clinical and personal perspective on three neurodegenerative diseases: ALS, Parkinson’s, and FTD.
Our patient guests put a human face on the diseases and the biological problems that these researchers are trying to crack, while the clinicians’ perspective brought focus to the gaps in our understanding of core biology and how they implicate clinical understanding of the disease. These talks were moving and motivating. Hearing the patients’ and family members tell their stories brought home what it’s like to live with these diseases and the urgency of the challenge. For many of the researchers, this was the first time they had heard a patient present at a scientific meeting, and a number of attendees told us that this experience profoundly changed their view of the diseases they are studying.
4. To overcome health disparities in neurodegenerative disease, we must involve affected communities
Science and medicine do not exist in a cultural vacuum, and neurodegenerative disease research is no exception. A keynote lecture from neuropsychologist Dr. Jennifer Manly of Columbia University highlighted the challenges in addressing health disparities in neurodegenerative disease research at multiple levels, including who is impacted by these diseases and how they are diagnosed and treated, and representation in clinical trials and cohort studies.
Dr. Manley’s work focuses on Alzheimer’s and related dementias, yet disparities are present across the spectrum of neurodegenerative diseases. In the case of Alzheimer’s, data from multiple studies have shown that in elderly populations, Alzheimer’s and dementia prevalence in African-Americans is increased significantly, compared to caucasians of the same age.
Dr. Manly’s talk dissected some of the reasons underlying these disparities, including the impact of social injustices, past and present. She also highlighted the tremendous challenges around registries and cohort studies, which, to date, are not representative of the general population and skew towards white, economically privileged, largely urban-based patients who come into the healthcare system and associated research infrastructure through major medical centers.
Dr. Manly challenged us all to think beyond the status quo and standard approaches for diversifying cohorts. She also pointed out that these disparities impacting patients and disease research are mirrored by disparities in representation in the scientific workforce and who is conducting the research, and the way that this lack of diversity may impact the types of scientific questions that get asked and the way that science is practiced. As we look to the future of the field more broadly, we see the importance of diversifying the scientific training pipeline and workforce and ways to create diverse and inclusive research environments.
5. Putting open science into practice takes work
Open science is core to our values at CZI.
We believe that sharing results, data, and resources, including software, code and also experimental tools, as early as possible accelerates the progress of science.
These open science principles are also baked into our grant agreements, evaluation and selection processes. Values and policies are, however, only a first step to operationalizing and putting open science into practice, and we recognize that practicing open science requires effort and is not without its challenges.
We organized a panel and open discussion around “Open Science in Practice” to discuss open data sharing, the value of preprints as a means to share results faster, and ways to share methods and resources with the broader research community through platforms like protocols.io and Addgene.
The sharing and dissemination of resources that the Challenge Network develops — tools, protocols, data and knowledge — with the broader research community is critical to how we see the Challenge Network impacting science in this field. Challenges around the current incentive systems in science, in particular around career progression and funding, were raised as barriers to open science adoption. Nonetheless, there was tremendous enthusiasm for open science, collaboration and sharing, and a palpable excitement about changing the culture of science.
The aspirational vision for CZI’s Neurodegeneration Challenge Network is a network that is more than the sum of its parts, and this vision for neurodegeneration builds on CZI’s approach to science overall — a strategy that proposes that collaboration, technology, and open science together are the keys to accelerating science and curing disease.
This first meeting for the Neurodegeneration Challenge Network is only the starting point. We have a lot of work to do and a lot to learn, and we can’t wait to see how this community develops and where their research and collaboration leads.
To learn more about our work in science and to stay updated on funding opportunities, visit our website, where you can sign up for our mailing list. You can also follow us on Twitter. To learn more about our science team, follow the CZI science blog. And you can always reach us at email@example.com.
Katja Brose, Science Program Officer, Chan Zuckerberg Science Initiative
Katja Brose, Ph.D., is a Science Program Officer at the Chan Zuckerberg Initiative, where she leads CZI’s efforts in neurodegenerative disease. She received her PhD from UCSF, where she studied developmental and molecular neuroscience. Prior to joining CZI, she was part of the editorial team at Cell Press, where she was Editor-in-Chief of the journal Neuron and a member of Cell Press management team. She is passionate about basic science and its potential impact for understanding and treating disease.