# Blue Ribbon Panel Highlights

## History of the NINDS Intramural Program

From its beginnings as the National Institute of Neurological Diseases and Blindness (NINDB), NINDS and its intramural program have had a history of supporting world-class researchers and building strong collaborations that have led to major, transformative discoveries. Established in 1950, NINDB was at first inseparable from NIMH, relying on NIMH for an initial budget, administrative support and sharing the same intramural program. Researchers were free to follow their interests and were not constrained by institute boundaries. Over time as the NIH IRP grew and vision (NEI) and communication research (NIDCD) were established as independent institutes separate from NINDS, the community of intramural researchers studying the brain and nervous system grew and became fragmented amongst several different institutes and buildings. Despite these administrative and physical boundaries, the neuroscience community at NIH maintained strong collaborations through shared projects, multidisciplinary interest groups and seminars, and shared core facilities. 

Bob Wurtz, the prominent NEI systems neuroscientist (National Academy of Sciences, Gruber Prize in Neuroscience) came to NIH in 1965 to the Laboratory of Neurophysiology jointly run by Wade Marshall in NIMH and Karl Frank in NINDB.  Wurtz describes the atmosphere surrounding the neurosciences in the IRP in his autobiography (The History of Neuroscience, Society for Neuroscience): “I quickly learned that names did not mean much, and that there was little relevance of which Institute you worked in”. Indeed, he wanted to work with Edward Evarts next but was picked up by Ichiji Tasaki’s laboratory in NIMH because Evarts did not have a position. Wurtz went on to become the founding Chief of the Laboratory of Sensorimotor Research in NEI in 1978 and remains active today, in what is still an outstanding group of investigators who use non-human primates to study the brain. This intense spirit of cooperation across Brain Institutes remains alive today as evidenced by a robust and highly interactive MRI program that supports work in all of the brain-focused Institutes.  Most visible is the new John Edward Porter Neuroscience Research Center. Completed this year, the building unites as many as 85 NIH neuroscience groups and 800 investigators under a single roof, further facilitating the kind of cross-cutting collaboration that has been a hallmark of the NIH IRP. Today the NIH IRP remains one of the largest biomedical research institutes in the world with over 1000 principle investigators. It is as much a remarkably collegial environment today as it was when Wurtz arrived, and this great breadth of biomedical research can be leveraged for exciting collaborations. A highly collaborative environment is a core value of the NIH IRP that we try and renew with each generation.   

The NINDS IRP has a strong legacy of supporting outstanding scientists and major breakthroughs in neuroscience. Among the first recruits to the IRP were Julius Axelrod (who initiated the modern study of neurotransmitters; received the Nobel Prize in Medicine in 1970), Daniel Carlton Gajdusek (who showed that kuru was a transmissible prion disease; received Nobel Prize in Medicine in 1976), Roscoe Brady (who uncovered the pathogenesis underlying Gaucher and Fabry diseases; received a Lasker award in 1982), and Kenneth Cole (who invented the voltage clamp technique; received National Medal of Science in 1967). W. King Engel, one of the IRP’s early clinical directors, introduced the use of corticosteroids for neuromuscular autoimmune disorders such as myasthenia gravis. Early NINDS IRP work on cochlear implants laid the groundwork for the extramural neural prosthesis program. The “Ommaya reservoir” was developed at NINDS and is named after Ayub Ommaya, the Chief of Neurosurgery at that time. Tom Reese (National Academy of Sciences) and his colleagues used electron microscopy to describe vesicle fusion for neurotransmitter release, the blood-brain barrier and to contribute to the discovery of kinesin. During his first few years at NIH, Wurtz describes interacting with fellow trainees Phil Nelson, Gerry Fischbach and Bob Burke, as well as hallway conversations with Mort Mishkin and Emilio Bizzi. The NINDS IRP remains a vibrant place for research and training with over 250 trainees. **The goal of attracting outstanding people, giving them freedom to produce exceptional science in a highly mentored environment remains a core value of the NIH IRP.**

The NIH boasts world-class resources to support it science. Wurtz worked in building 9 where he took advantage of shop facilities to engineer a rig for recording neural activity from awake behaving non-human primates using equipment designs pioneered by Evarts. Wurtz’ work involved recording from head-fixed animals to monitor neuronal responses during saccades and this launched his independent career. Indeed, the shared shops jointly run by NIMH, NINDS and NICHD are assets that remain as important today as they were then.  Access to remarkable facilities remains a core value of the NIH IRP. The flagship of shared resources in the IRP is the NIH Clinical Research Center that remains the largest clinical research facility in the world, allowing researchers to treat and study patients from all over the world, independent of the United States health care system. A core value that we will continue is to maintain, despite increasing budget pressures, exceptional facilities for performing research in the NINDS IRP and across the NIH IRP.

A truly unique feature of the NIH IRP is its close proximity to the Institute Director and extramural staff of the Institutes inside the Washington Beltway. The IRP is the face of the biomedical research work funded by NIH and it hosts frequent visits from Congress and the White House where the visitors can experience science in action. Individual PIs in the IRP and their work can influence programs for the entire nation. For example, Kenneth Fischbeck played a role in formation of the spinal muscular atrophy trial network, which influenced Petra Kaufmann when she established NeuroNEXT as a network for excellence in neuroscience clinical trials. As government employees, we are stewards of the public’s investment in biomedical science. Strict Federal ethical standards require that the IRP be able to provide advice and data that are free from financial conflicts of interest. A core value of the NIH IRP is to take the time and care to get the science right with an emphasis on solving problems that may take a long time trajectory.

Today, the NINDS IRP remains highly active and collaborative, spanning basic and translational neuroscience, neurology and neurosurgery. The program maintains its historical strengths in neuromuscular diseases, neuroimmunology, membrane biochemistry and biophysics, neurophysiology on the system and synaptic level, and we are beginning to provide an infrastructure for the bidirectional flow of knowledge and discovery between clinical and basic research. NINDS also continues its robust training programs for postdoctoral and clinical fellows as well as undergraduate and graduate level students. The NINDS IRP strives to renew and embody all of the core values that we think distinguish the NIH IRP (See: NIH IRP at the Threshold of a New Era, 2009, separate attachment). This material is provided to the Blue Ribbon Panel to summarize the state of the NINDS IRP in 2014 with an eye toward helping to set strategies for the next decade of development.

## Neuroscience research across the NIH Intramural Program

Few areas of biomedical research funded by the NIH are growing as rapidly as neuroscience. In the extramural program for example, NIH as a whole spent $5.3 billion on neuroscience research in fiscal year 2013, surpassing cancer research spending for the first time in history. The NIH intramural program is home to a large neuroscience research community, composed of more than 170 laboratories within 12 Institutes and Centers including the National Eye Institute (NEI), National Human Genome Research Institute (NHGRI), National Institute of Child Health and Human Development (NICHD), National Institute of Dental and Craniofacial Research (NIDCR), National Institute of Environmental Health Sciences (NIEHS), National Institute of Mental Health (NIMH), National Institutes of Neurological Disorders and Stroke (NINDS), National Institute of Aging (NIA), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute on Deafness and Other Communication Disorders (NIDCD), National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK), and the National Institute on Drug Abuse (NIDA). The research in the NIH intramural neuroscience community spans basic, translational and clinical neurosciences across a broad range of fields including biophysics, molecular and cellular neurobiology, synapses and circuits, neuronal development, brain imaging and neurological and psychiatric disorders. The neuroscience intramural programs also provide extensive pre- and postdoctoral training opportunities, and host multidisciplinary seminars and interest groups on topics such as drosophila neurobiology, membrane proteins, neuroinformatics, PET, structural biology, and synaptic and developmental neuroplasticity.

With the recent completion of the Porter Neuroscience Research Center, laboratories from nine NIH institutes with neuroscience interests are now housed under one roof within Porter, where a balance is struck between grouping principal investigators by common interests or resources independent of Institute as well as maintaining strong interaction within an institute. NINDS 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, administering the Porter building, and leading several trans-NIH core facilities such as the NIH 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 that is available to any PI at the NIH. 

## Executive Summary

****Scientific****Program****The NINDSIntramural Research Program (IRP) is an active group that spans basic neuroscience, translational neuroscience, neurology and neurosurgery. Presently, there are 46 tenured/tenure track PIs at NINDS organized as independent units/sections or operating as part of laboratories or branches. During the past five years, about 250 manuscripts per year were published from the NINDS IRP. Of those, about 10 percent appear in the highest impact journals.  PIs in NINDS have 89 active human protocols, 82 active animal protocols, file an average of~22 patents annually, and have 17 active collaborations with industry. The PIs supervise about 60 staff scientists/staff clinicians who run our research facilities and clinical services or reside within specific programs to support research activities. During the past eight years, 21 PIs have left NINDS and 14 new PIs have been recruited. This contraction of the NINDS IRP is also evident at most of the other institutes’ IRPs. Budget pressures and larger group sizes per PI required to meet Board of Scientific Counselors recommendations have contributed to the shrinking number of PIs at NINDS. Strategies to improve collaboration among PIs and encourage high-risk research include a New Initiative Program that provides incentives to PIs who collaborate on projects or undertake a new project. A major goal in the next five years is to achieve a critical mass of physician scientists in clinical areas such as neurosurgery, stroke and movement disorders with central resources in the Office of the Clinical Director used to make these groups more cohesive. A second goal is to become a recognized site for conducting first-in-human clinical trials. Regarding basic science research, we will continue to recruit outstanding PIs in neuroscience areas of relevance and to identify mechanisms that better leverage interactions with PIs across NIH.

****Training and Early Career Development****The NINDS IRP has about 260 trainees at the graduate, postdoctoral and clinical fellow levels.  About 15 years ago, NIH formalized its graduate student training through the creation of Graduate Partnership Programs. NINDS PIs are among the most active at NIH in training graduate students, with about 34 presently pursuing their PhD at NINDS. NINDS maintains long-running and successful programs that provide summer research experiences for undergraduates and 1-2 year full time research experience for post-baccalaureates between college and graduate/medical school. Major goals in the next five years will be to continue to recruit outstanding trainees at all levels, continue to build critical mass in clinical training and to increase racial/ethnic/gender diversity across the program.

****Research Facilities****NINDS manages a number of research support facilities. These include a large and active animal program, a bioinformatics group, and facilities housing light microscopy, electron microscopy, protein mass spectroscopy and flow cytometry. Recently, we purchased new equipment for the light microscopy, flow cytometry and mass spectroscopy facilities. Moving forward, we will maintain these facilities as state-of-the-art resources and will consider new facilities, such as an advanced 3D histology/array tomography core, as needed.

****Clinical Services and Interactions with the NIH Clinical Research Center****NINDS manages a number of clinical services in support of NIH-wide clinical activities in the Clinical Center, as well as specific neurological disease clinics. This critical infrastructure supports 89 active clinical protocols. Some of these services are managed by the Office of the Clinical Director and can be used by any PI at NIH. Dr. Avindra Nath, Intramural Clinical Director at NINDS continues to improve the overall management of the institute’s central clinical resources. These include a neurology consult service, EMG clinic, EEG/sleep clinic, Parkinson’s clinic and a neuroimmunology clinic. A variety of disorder-specific clinics are run by PIs or branches such as the movement disorders clinic and the neurogenetics clinic. About half of the services provided by the Surgical Neurology Branch are performed in support of branch specific protocols, the other half are performed in support of the Clinical Center. A challenge for these services is the recruitment and retention of outstanding staff clinicians. A new Center for Translational Neuroscience, directed by Dr. Nath, has been formed to assist PIs with high-throughput screening, differentiation of stem cells, and proteomics of CSF for potential biomarkers in trials.****

****Participation in Trans-NIH Programs****

NINDS has enthusiastically supported trans-NIH intramural facilities and programs.  This tradition began when Dr. Landis, as the institute’s Scientific Director, assumed responsibility for administration of the NIH MRI research and mouse imaging facilities. NINDS is the lead institute for the NIH Intramural Neuroscience Program, administering the Neuroscience@NIH website and the weekly Neuroscience Seminar Series. NINDS manages the John Edward Porter Neuroscience Research Center, which integrates PIs from nine institutes, and requires balancing each institute's space allocations with the goal of organizing investigators along scientific themes. A major 5-year objective will be to get the John Edward Porter Neuroscience Center fully operational. In addition, NINDS continues to administer the NIH MRI research, mouse imaging and human stem cell facilities, and supports the National Center for Regenerative Medicine, the bone marrow stem cell facility and the Center for Human Immunology. NINDS also has created a Parkinson's Disease Working Group and runs a Parkinson's clinic available to any PI at NIH to encourage investigators from across the IRP to work more closely together on Parkinson’s research.   

****Budget, Space and Administration****

****Budget**: The budget for fiscal year 2014 is **$156 million.****Roughly a third goes to central NIH costs including the Clinical Center, a third runs NINDS facilities including the Clinical Program and the Animal Program, and about a third goes directly to the PIs. About ten percent is needed to administer the program. Flat budgets and rising central costs for management of the NIH and Clinical Center have stressed the NINDS budget. Over the past two years, cuts in the IRP budget because of the US government wide sequester, led to a 6.6 percent across-the-board cut to the tenured intramural NINDS PIs. Even though our budget has been constrained, we have been able to fulfill the recommendations of the NINDS Board of Scientific Counselors for additional resources for outstanding investigators and to continue hiring new PIs. There are two reasons for the relatively small impact of budget pressures. First, the program continues to shrink. At the time Dr. Landis took over as Scientific Director in 1994 there were more than 65 PIs as compared to 46 at present. Second, we have aggressively sought out administrative efficiencies. More than $4.7 million in ongoing savings have been realized over the past five years by aggressive use of IT systems, renegotiation of high overhead contracts and replacement of phones with VOIP. Further efficiencies require a trans-NIH effort to improve processes across the entire IRP. Over the next five years we will push for an effort to find efficiencies in central management of the NIH IRP.  

******Space:******The NINDS IRP occupies 120,798 sq. ft. of space in three major sites at NIH: the Building 10/Clinical Center complex, Building 49 and the John Edward Porter Neuroscience Research Center. NINDS space has undergone major changes due to the recent completion of the Porter Neuroscience Research Center and the revitalization of Building 10. Indeed, our physical space is in outstanding condition. Over time, we have been able to consolidate and better integrate space in the Clinical Center complex, as well as maintain the scientific and thematic approach to allocation of space in the Porter Neuroscience Center. Space is not a constraint on future program development. Budget and our ability to recruit outstanding people within the constraints of government positions are more serious limitations. If budget pressures continue, a major challenge will be to make effective use of the new space that has become available with completion of the Porter Neuroscience Center.

******Administration:******The NINDS has a strong administrative support team. Dr. Alan Koretsky has been Scientific Director since Fall 2007. He is assisted by a number of outstanding staff. Peggy Rollins runs the Office of the Scientific Director that oversees management of the entire NINDS IRP and in particular she administers Board of Scientific Counselor reviews, PI recruitment and competitive fellow applications. Laurie Jarvis, the Chief Administrative Officer (AO), oversees administration, purchasing, property and the office manager pool.  During the past four years, she has led an effort to benchmark workloads across the administrative staff, enabling us to better assess performance and to find efficiencies. We have invested in a strong information technology (IT) and internet development team led by Dr. Yang Fann. With their help, we are in the process of converting all administrative processes to a paperless system that has enabled better tracking and improved efficiency. Dr. Rita Devine manages space, the Porter Neuroscience Research Center and the summer undergraduate research program. Finally, Dr. James O’Malley manages a large and active animal program that consistently receives top ratings, according to AALAC reviews. During the next five years, we will continue to modernize our administrative processes with the development of web-based tools. The increasing reliance on information technology has led us to develop the ‘next generation’ Administrative Officer who understands a broader range of administrative processes, can help develop web-based tools, while also capable of navigating the complex workings of NIH. 

******Strategic Planning and Long-Term Vision******The NINDS IRP will continue to maintain its strengths in basic neuroscience and translational neuroscience. On the basic end of the spectrum, an excellent group pursing structural biology and biophysics has reached a critical mass especially when including PIs from other institutes. Membrane proteins, cytoskeleton and synaptic structure are all areas of strength. Similarly, the synaptic/circuit group represents a longstanding asset that benefits significantly from neighboring PIs in other neuroscience institutes. Linking synaptic structure to circuit calculations may be an area to target for future hiring. The goal of the Cell and Developmental Neuroscience group will be to continue to build this group with PIs that have a dual interest in fundamental cell and developmental biology, as well as mechanisms of neurological diseases. The work of this group dovetails with that of PIs from NICHD and NIDCD who have recently moved into the Porter Neuroscience Center. NINDS is committed to recruiting and developing exceptional physician scientists. Roughly 3 to 5 physician scientists will be sought in the areas of neurogenetics, neuroimmunology and neurovirology, stroke, movement disorders, and surgical neurology. A goal will be to develop a central infrastructure to become a premier site for first-in-human trials of treatments for neurological disorders and stroke. A key long-term challenge will be to develop mechanisms that enable our clinical program researchers to collaborate with our neighboring hospitals and medical schools in a seamless manner.