The National Institute of Neurological Disorders and Stroke (NINDS) recently convened its first Blue Ribbon Panel to review the NINDS IRP and provide feedback on how to build upon the program’s strengths, leverage opportunities, and overcome challenges, with the overall goal of enhancing the program’s contribution within the larger scientific community. The NINDS Blue Ribbon Panel was chaired by Dr. Robert Darnell (Heilbrunn Professor and Senior Physician, Rockefeller University, HHMI Investigator, and President, NY Genome Center) and consisted of nine other extramural experts with a broad perspective on basic neuroscience and clinical neurology and considerable knowledge about NINDS.
The mission of the National Institute of Neurological Disorders and Stroke (NINDS) is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. The NINDS fiscal year 2014 budget was approximately $1.58 billion with about $1.3 billion going to extramural grants and contracts, $58 million to Research Management and Support for extramural programs, and $156 million (9.8 percent) going to the Intramural Research Program. The NINDS IRP consists of 46 tenured or tenure-track principal investigators who supervise approximately 60 staff scientists and clinicians and over 250 trainees including graduate students, and postdoctoral and clinical fellows. The program places emphasis on recruiting and developing exceptional investigators, facilitating outstanding and collaborative neuroscience, enabling translation from bench to bedside and back, and training the next generation of neuroscientists.
The program spans basic and translational neuroscience, neurology, and neurosurgery and maintains its historical strengths in neuromuscular diseases, neuroimmunology, membrane biochemistry and biophysics, and neurophysiology on the system and synaptic level. Areas of strength in basic neuroscience include: ion channel/transporter/cytoskeleton structure and function, mechanisms of synaptic function and structure, and genetic/cell/developmental processes that underlie neurological disorders. Imaging research entails a broad spectrum of resources, from state-of-the-art electron microscopy and light microscopy to an active research program that develops and applies next-generation MRI technologies. Specific clinical focus areas are: neurogenetics, neuroimmunology, neurovirology, movement disorders, stroke, and surgical neurology.
The quality of the science at NINDS is excellent, and has been improving over the years during the tenure of Dr. Landis and the scientific director, Dr. Koretsky. High-risk projects, as well as explorations of new areas, are encouraged and tenured faculty take advantage of this. While we recognize the importance of clinical and translational research in understanding neurological disorders and advancing new therapies, and the need for an enhanced focus in this area, the nature of our understanding of brain function also requires a continued focus on the basic sciences. With that in mind, we feel that the NINDS leadership should be commended for their steadfast investment in the basic neurosciences, and the Panel enthusiastically supports a continued investment in pursuing this strategy toward understanding brain development and function. We also support efforts to relate this effort to the development of therapies and cures for brain disorders. We hope the strong support of basic research will not be lost in the drive towards enhanced utilization of the Clinical Center and translational studies.
Overall, the strengths of the NINDS IRP can be summarized in four points: outstanding leadership, integrative science within NINDS and between IRPs, outstanding support for basic science in the context of the clinical mission, and vigilance on opportunities to strengthen and expand that clinical mission.
Distinctive features of the NINDS IRP program structure include: 1) a flat structure with resources going directly to individual PIs based on rigorous external review by the BSC; the philosophy that these reviews are weighted toward recent past performance is highly commendable; 2) a high bar for recruitment of outstanding PIs, with a special focus on recruitment of junior faculty, women and minorities; 3) a Special Initiative Program that gives supplemental funds for new and collaborative research projects that are instigated by investigators.
A bedside-to-bench-to-bedside approach guides the program, which has made significant strides in neurogenetics and neuroimmunology. Another major strength of the current program is that several senior investigators have taken advantage of the unique stable funding environment at the IRP to move fluidly into new, potentially risky areas. This is underscored by consideration of the outstanding nature of the NINDS intramural scientific program, which is internationally recognized in a number of areas, including imaging, channel function and physiology, and neurogenetics.
The leadership of NINDS is by all criteria exceptional. Dr. Landis, both in her previous role as scientific director (SD) and her current role as Institute Director, has reshaped the institute in many positive ways. Specific to this review, she has reinvigorated the Board of Scientific Counselors (BSC), which now quite effectively provides a rigorous and comprehensive retrospective review of intramural investigators, and supported the growth and leadership of the current SD, Alan Koretsky.
Under the leadership of Dr. Landis and Dr. Koretsky, NINDS was the key Institute behind completing the building of the Porter Neuroscience Research Center, which will house 85 laboratories from 9 Institutes. This state-of-the-art research building, which NINDS now administers, represents visionary thinking and has been viewed as a highly successful opportunity for interactions between Institutes. NINDS also plays a lead role in fostering collaboration and coordination across the neuroscience community at NIH by organizing the Monday noon Neuroscience lecture series, hosting the Neuroscience at NIH website, and leading several trans-NIH core facilities such as the NIH Nuclear Magnetic Resonance (NMR) Research Facility in the NIH In vivo NMR Center, and the Human Stem Cell Facility. Other examples of NINDS-led initiatives for the NIH Intramural community include a Trans-NIH Parkinson’s Disease Clinic and Working Group.
Resources within the IRP have been demonstratively redirected away from less productive investigators and towards more productive investigators and new recruits. This has led to a significant turnover of faculty, with less productive faculty winding down their programs, and new, young outstanding investigators being recruited to the IRP using international open searches. Overall, it was felt that over time the balance between tenured and non-tenured investigators should continue to be shifted more towards younger investigators. At the same time, the BSC, working with the leadership team, can further facilitate the move to support the strongest and most creative science by continuing to redirect funds away from labs that are not engaging in innovative, collaborative research. Overall, the leadership has done a good job in recruiting very strong and in some cases world-class basic neuroscientists. Moving forward, the leadership group should be encouraged to continue to set a very high bar for the quality of new recruits. In addition, the current portfolio of tenured and untenured faculty (~3 to 1) should continue to be rebalanced toward junior faculty.
Support existing strengths
Several features distinguish the IRP programs in general and NINDS in particular. Stable funding has been a key variable in being able to attract some of the best neuroscientists in the country to the NINDS IRP, including recent junior hires, and retention of senior hires. The completion of the Porter Neuroscience building has been an important addition to this strength. Going forward, integration with the Clinical Center, for example through the in vivo NMR center, offers ongoing chances to connect science and clinical medicine, as does the lack of barriers between NINDS and other Institutes.
Support integrative, synergistic science
NINDS has served as a catalyst in tearing down barriers within the IRP. This presents both a challenge and an opportunity. The amount of extra work required to reach out is not insignificant, and NINDS has done this through its philosophy and its actions, including fostering collaborative inter-institutional science, development of a neuroscience web site and a Monday seminar series, and through its role at the Porter Neuroscience building.
Strengthen Clinical Center
The challenge and opportunity of deep integration with the Clinical Center is well recognized by NINDS. A fully objective outside review, along the lines of this NINDS IRP review, is seen by this Review Panel as a crucial step toward such integration.
Below is a list of 15 specific recommendations from the Blue Ribbon Panel.
1) Make NIH Clinical Center more accountable
Make the Clinical Center budget more transparent by making it a separate line item in the Congressional budget. The Clinical Center would also benefit substantially from an independent, transparent BSC-style review of its scientific and clinical programs, as well as its operations and management.
2) Recruit at least five top-tier physician-scientists
The IRP would benefit from a better balance of basic and clinical science. We recommend tenure track recruitment of at least five top-tier physician-scientists focused on neurologists and neurosurgeons. Success in such recruiting will benefit from leveraging the strength and stability of IRP funding, the collaborative environment established for interdisciplinary science, and the Clinical Center.
3) Recruit more women and minorities to positions in IRP
NINDS should intensify its efforts to recruit women and minorities to positions in the IRP, noting that, as in all of the NIH, these individuals are substantially under-represented at NINDS. One suggestion is to learn from and expand upon the successful outreach strategies used to recruit talented minority candidates to the IRP’s summer fellows program.
4) Capture phenotypic, genetic, and biomarker data on all research subjects
The breadth of patients seen in the NIH Clinical Center makes it very well suited to collect phenotypic, genetic, biomarker and imaging data on all research subjects. The Clinical Center, and especially that component related to NINDS, would benefit from developing the infrastructure for routine sequencing, informatics and imaging.
5) Develop robust bioinformatics infrastructure
All of the biological and imaging data that could be generated from Clinical Center patients (see recommendation number 4) can be a resource for basic scientists in hypothesis generation. The Institute should develop a more robust infrastructure and hire more bioinformaticians to develop tools for data storage and analysis.
6) Identify all disease genes
Because many disease genes involve the central nervous system, NINDS should be a leader in the effort to identify all the genes tied to brain disease.
7) Fill gaps in development of treatments for rare neurological diseases
Big Pharma is increasingly focused on Rare Diseases, but have withdrawn from many psychiatric and some neurological diseases. NINDS IRP should help fill this gap.
8) Improve patient recruitment
The IRP should hire a clinical trials coordinator devoted to promoting trials to patient groups and local doctors and hospitals.
9) Provide trainees with more opportunities for collaboration and development
The IRP should foster additional interactions among trainees, give them more opportunities to participate in planning activities, and provide training in writing IRB protocols.
10) Increase collaboration between the basic science program and the clinical program
The right infrastructure for genomics and computational biology could help close the gap between the clinic and the bench.
11) Expand opportunities for collaboration with the extramural community
NINDS intramural investigators should be encouraged to seek out appropriate collaborations with the extramural community as well as intramural investigators within and outside the NINDS. Also, NINDS should take the lead in synergizing the intramural and extramural neuroscience community in areas of particular strength.
12) Vary lab group size to reflect needs of different domains
Larger groups of 12 to 15 might be more effective for some approaches to molecular, cellular and genetic studies related to neurological diseases, as such labs may require a broad range of expertise. In addition, we suggest select consideration of larger group sizes for young investigators as they ramp up their research programs.
13) Better Utilize the Porter Neuroscience Building
Use of inter-Institute shared funding for additional recruits to fill Porter Neuroscience Research Center should be encouraged.
14) Consolidate efforts in neuroscience across the NIH
Create formal mechanisms for establishing NIH-wide priorities in nervous system research among the twelve Institutes that sponsor research relevant to diseases of the brain.
15) Science Synergy
A continued vision toward synergistic science, particularly in the era where multidisciplinary science is increasingly important, will be an important future direction. We believe that many of the suggested recommendations, particularly these last two, will require a significant increase in NINDS funding, which would be an appropriate recognition of the leadership NINDS has brought to the IRP community and to medical neuroscience more broadly.