EDITORIAL

Neurology’s Stake in FoundationalNeuroscience Research

The National Institutes of Health (NIH) mission is toseek fundamental knowledge about the nature and

behavior of living systems and the application of thatknowledge to enhance health, lengthen life, and reduceillness and disability. For over a decade, the NationalInstitute of Neurological Disorders and Stroke (NINDS)mission statement focused on reducing the burden of ill-ness due to neurological disorders. Although the need forbasic research as part of this mission was always implicit,a recently released analysis of NINDS grant applicationsconvinced leadership to make it explicit by adding“advancing fundamental understanding of the nervoussystem” to our mission statement (http://www.ninds.nih.gov/about_ninds/message/message-back-to-basics.htm).

NINDS believes that the taxpayer’s investment inneurological health is best served by funding the best sci-ence across the full spectrum of basic, translational, andclinical research. However, our analysis revealed a con-cerning drop in proposals that focused on understandingthe fundamental mechanisms of neural function; the rateof decline between 1997 and 2011 indicated that by2025, NINDS might have zero funded applications forfundamental neuroscience research (http://blog.ninds.nih.gov/). We do not yet know what accounts for the declinein basic research applications. The NINDS analysis dem-onstrated that basic neuroscience applications scored bet-ter in peer review than other types. Has the researchgravitated to other neuroscience institutes at NIH? Isthere a perception that NINDS prefers disease-focusedresearch? For example, we realize that NINDS initiativeshave generally focused on gaps in disease research, whichmight suggest a preference for disease-focused, asopposed to basic, research. Of course this is not the case.We are committed to supporting a balanced portfolio ofbasic and disease-focused research. We must acceleratethe translation of basic research findings into interven-tions that will benefit patients, but if fundamental basicresearch investigating the normal nervous system contin-ues to decline, the pipeline that makes translation possi-ble will be compromised.

NINDS supports research on the hundreds of dis-orders, both common and rare, that affect the nervoussystem. Neurological disorders impair those faculties thatare intrinsic to human nature and prevent affected indi-viduals from fully participating in society. Deterioration

of brain function affects almost everyone who survives toold age, making neurological disorders personal for mostpeople. The burden and nature of neurological illnessattracts many researchers to the challenge of understand-ing and developing treatments, and the NINDS portfolioanalysis showed healthy growth in basic research on dis-ease mechanisms. Brain science also appeals to the pureinquisitiveness in bright scientists who are driven toexplore the last great frontier in biomedical research—understanding brain function and the underlying neuralprocesses that make us human. These two directions inbrain science are inherently complementary. Greaterknowledge of the neural underpinnings of normal brainfunction would greatly inform our understanding of neu-rological disorders, by setting a foundation for askinghow disorders alter known normal functions. It can beargued that our ignorance of basic neural mechanisms isat the root of recent failures to translate discoveries fromdisease research into new therapies. From remarkablegenetic discoveries of the past few decades, we know themutations that cause many diseases, and we have identi-fied the mutated proteins. Yet so far we have achievedlimited success in turning these advances into effectivetreatments, largely because we do not fully understandthe underlying biology. Multiple phase 3 neuroprotectiontrials in a variety of disorders have confirmed that ouroriginal expectations were too simplistic; the basic biol-ogy has proven to be more complex. As a consequence,our problems are considered too difficult by many of themajor pharmaceutical companies that have recentlyclosed their central nervous system developmentprograms.

Amazingly, some of us practiced neurology beforemagnetic resonance imaging, and are acutely aware hownew tools have transformed the efforts of researchers andclinicians and have benefited patients. We clearly needbetter tools to solve some of our most vexing researchchallenges, and based on the explosion in science tech-nology we can count on their arrival. Exciting new toolshave been coming at a constant clip from basic researchlaboratories, but we will need to maintain an investmentin fundamental basic research for this momentum tocontinue. One of the most important recent advances inneurological disease research, induced pluripotent stemcell technology, came from very basic developmental

Published 2014. This article is a U.S. Government work and is in the public domain in the USA 621

biology. Optogenetics came from studies of the light-activated membrane channels in single-cell organisms,and hundreds of investigators are now using this technol-ogy to dissect how neural circuits work. The BRAIN(Brain Research through Advancing Innovative Neuro-technologies) initiative (http://www.nih.gov/science/brain/)is a program designed to foster the development of morenew tools that will enable a better understanding of brainfunction and brain disorders.

NINDS hopes to motivate bright PhD and MDscientists who are drawn to understanding nervous sys-tem function to follow their scientific curiosity. We seetremendous value in all aspects of our grant portfolioand perceive the different kinds of research within it asintegrated and synergistic. Basic neuroscience has alwaysbeen the foundation from which we explore diseasemechanisms and devise treatments for patients. Neuro-physicians and their patients are essential advocates forneuroscience research, and we hope they will considerlending their voices to promote basic neuroscienceresearch, both for its intrinsic value and for its potential

to open doors to new treatments for neurologicaldisorders.

Potential Conflicts of Interest

Nothing to report.

Walter J. Koroshetz, MD

Story Landis, PhD

National Institute of Neurological Disorders and Stroke

National Institutes of Health

Bethesda, MD

Acknowledgment

Dr. Amy Adams, Christine Torborg and Anna Taylor for

their contribution to this article.

DOI: 10.1002/ana.24161

ANNALS of Neurology

622 Volume 75, No. 5