Q&A: NINDS Acting Director Discusses Challenges, Priorities for Institute

Walter Koroshetz became acting director of NINDS in October 2014. Previously, he served as deputy director under Story Landis. He has held leadership roles in several NIH and NINDS programs, including the BRAIN Initiative.

NQ: What are your priorities for NINDS and what do you see as the institute’s biggest challenges as you step into your role?

Under Dr. Landis’ leadership, NINDS was seen as a fair and transparent funding agency that engendered the trust of our multiple stakeholders: the neuroscience community, neurological disease-related organizations, and professional societies, particularly SfN. My goal is to maintain and build upon this trust by ensuring that every federal dollar invested is optimally allocated. NINDS staff care deeply about neuroscience and always strive to make the right decision, especially when faced with a challenging fiscal environment. NINDS must be an excellent steward of taxpayers’ investment in neuroscience and neurological disorders. This means improving how we train and fund superb scientists, stimulating scientific dialogue, providing necessary infrastructure, aligning incentives with broadly supported goals, and disseminating the great science produced by our funded investigators. We will be able to take on big challenges if we have the discipline and dedication necessary to integrate NINDS into the fabric of U.S. neuroscience and the battle to help those suffering with neurological disorders.

NQ: What are the next steps for the BRAIN Initiative and how is NINDS interfacing with other NIH institutes, federal agencies, and business partners to achieve the initiative’s goals?

The BRAIN Initiative is quite remarkable, as the impetus for this ambitious effort came from the president of United States. Now the BRAIN Initiative is receiving international attention, with countries each taking different approaches, and it’s interesting to see how these various efforts are complementary. The U.S. initiative focuses on the development of technologies for neuroscientists working to understand neural circuits. The scholarly approach recommended by the NIH’s Advisory Committee to the Director as outlined in BRAIN 2025: A Scientific Vision is a must-read. In a simplified view of the BRAIN pipeline, NSF grantees from the physical sciences and engineering complete the critical upfront work, NIH grantees develop and test applications of new technologies in neural tissue, and DARPA grantees apply these technologies to solving clinical problems of importance to our veterans. Partnerships with industry are still in the nascent stages. From the NIH viewpoint, we want to harness powerful tools in informatics, signal detection, pattern recognition, and materials science for the challenges that our investigators will be attacking.

NQ: As neuroscience becomes increasingly “transdisciplinary,” drawing on many other fields, leaders are thinking about the evolution of scientific training. What are NINDS’ short- and long-term priorities and programs in this area?

NIH is intensely interested in how we can engage with the science community to best train the next generation of neuroscientists. My own entry to neuroscience was through biophysics, so early on I saw the advantages of bringing mathematical modeling, structural chemistry, computer engineering, and optics to bear on fundamental problems in neuroscience. Even in my clinical research career, it was the collaborations with geneticists, MRI physicists, and engineers that enabled the breakthroughs. We can’t predict which transdisciplinary links will turn out to be critical for neuroscience trainees, so they must cultivate a receptive and disciplined approach that will allow exploration of new scientific areas and techniques. Neuroscience training programs may need to partner with other science departments and develop special tracks for trainees so they come out highly skilled in both neuroscience and a sister science.

NQ: Another issue that has received a lot of attention is scientific rigor and methodological approaches in the field. What are the main concerns in this area and how are NINDS and NIH tackling the issue?

There is nothing like failure to make one re-examine one’s processes. I was involved in the neuroprotection stroke trials in the 1990s in which hundreds of millions of industry dollars were invested in following the story of glutamate excitotoxicity in ischemic injury. In 1999, after the debacle of failed trials, the stroke community took a hard look at the preclinical data and made recommendations called the “STAIR criteria” for rigorous methodology in preclinical studies, but the message never moved out of the stroke field. Now reports on the difficulty of reproducing novel findings have created momentum among many different fields of neuroscience. Shai Silberberg at NINDS has been an important leader in promoting transparent reporting of methods in publications and NIH grant applications. Dissemination of good laboratory practices and a greater understanding of statistics will do much to decrease practices that occur by chance. However, I think the problem of translating “therapeutic” results from animal to human studies is much more than a methodological one. Robustness and generalizability of the beneficial effect across varied experimental conditions, strains, species, genders, ages, etc., are issues that have to be approached in a rigorous fashion before investing in resource-intensive translational and clinical studies. Most critical is the need to develop objective measures that test whether an agent given at a specific dose and duration has the intended biologic effect in humans, i.e., “hit the target.” Without the latter, the human brain is treated like a “black box” when the leap is made from animal to patient studies. In its translational program, NINDS will invest in research to better estimate the value of potential therapeutic agents, whether tests of reproducibility, robustness, or markers of biologic effect in humans.

NQ: NINDS has placed a priority on diversity in the scientific workforce. What efforts is NINDS undertaking in this area?

Diverse backgrounds make for stronger teams. NIH is the taxpayers’ investment in biomedical research, and the recipients of those funds should reflect the diverse makeup of our citizens. In addition, one of our clinical missions is to reduce the tragic disparities in neurologic health in our country, and a diverse workforce is essential in this effort. Since the 1990s, NINDS has worked to enable students of diverse backgrounds to train in neuroscience and advance into impactful positions. The Enhancing Neuroscience Diversity through Undergraduate Research Education Experiences (ENDURE) program, in which we partner with SfN to support young trainees, is clearly successful. We are proud of the various programs administered by our Office of Training, Career Development and Workforce Diversity. Despite our activities to promote diversity in the neuroscience workforce, we remain disappointed that so few diverse trainees progress on to independent NIH funding. We are committed to working creatively to come up with effective programs aimed not only at the entry level but also at the hypercompetitive level of securing independent RO1 funding.