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Post by Former NIMH Director Thomas Insel: Investing in Innovation

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A recent symposium recognizing new and past recipients of NIH’s Pioneer Awards provided great examples of the pay-off from NIH’s investment in innovative science. The Pioneer Awards are but one example of the mechanisms now in place to support innovation. The New Innovator awards, the Transformative R01 (TR01) program, EUREKA, and the BRAINS awards were all designed with the aim of supporting unconventional, high-risk, high-reward research.

In addressing the recipients, NIH Director Francis Collins said that Pioneer Awards are aimed at helping scientists make new discoveries that will “change the way we approach science.” Funding is provided for up to $500K per year for 5 years, following a brief application and successful interview with a review committee. Since their inception in 2004, Pioneer Awards have covered vast areas of science, from technology development to epidemiology. Importantly, these awards support an individual rather than a specific project.

Three neuroscientists who received their funding in 2005 led off the symposium, describing insights into synaptic function and brain circuits achieved over 5 years of Pioneer funding.

  • Giulio Tononi at the University of Wisconsin-Madison Medical School described findings that support the hypothesis that sleep’s restorative function has to do with the costs to the brain of strengthening synaptic connections, which takes place during learning while we are awake.
  • Karl Deisseroth at Stanford University described what he called the “rapidly expanding toolkit” in optogenetics, a means of using genetic techniques to introduce light-sensitive proteins into neurons. The approach enabled observations described recently in Nature of the effect on brain circuit function from selectively inhibiting or stimulating a specific class of neuron.
  • Hollis Cline at the Scripps Research Institute in San Diego reported on the approach her team has developed that allows them to track how synapses form, and to observe how visual stimulation increases synapse formation.

In another example of innovative work supported by the Pioneer Awards, Steven McKnight, University of Texas Southwestern Medical Center, Dallas, and Pioneer awardee in 2004, recently reported discovery of a compound that restores the capacity to form new memories in aging rats (Pieper et al, Cell, 142: 39-51, 2010). 2007 awardee Peter Bearman has used the support to investigate the role of social and environmental factors in autism. He has reported provocative findings on the contributions of social changes on the risk of autism (Liu et al, Demography, 47:327 – 343, 2010).

NIMH scientists are also doing exciting research with support from other programs developed to support innovation. The NIH Director’s New Innovator Award Program aims at stimulating highly innovative research from promising early stage investigators. Awards are up to $1.5 million over 5 years. Examples of this program’s funding for NIMH-relevant projects include awardee Lauren A. Weiss, University of California, San Francisco, who is establishing stem cells to investigate autism-related mutations. Frances A. Champagne, Columbia University Morningside, is investigating the role of epigenetics—inherited changes in gene expression unrelated to DNA sequence—in transmission across generations of variations in maternal care and their impact on reproductive behavior in mice. Alan Jasanoff, Massachusetts Institute of Technology, is using this program’s support to develop protein-based sensors, targeted to specific cell types, and incorporating MRI contrast agents, that permit the monitoring of neural activity across the entire brain.

The NIH Director’s Transformative Research Projects Program was specifically created to support exceptionally innovative, high risk, original and/or unconventional research projects that have the potential to create or overturn fundamental paradigms. These projects tend to be inherently risky, but if successful can have a profound impact on a broad area of biomedical research. Support can be up to $25 million per year over 5 years, although most projects are much smaller. Grantee Partha P. Mitra, at Cold Spring Harbor Laboratory, received funding to generate the first brain-wide wiring diagram of mouse. Marius Wernig and Thomas C. Sudhof, Stanford University School of Medicine, are developing methods to generate neurons from non-neuronal cells, with the aim being a way to explore the effects of mutations associated with neuropsychiatric disease.

The Pioneer, New Innovator, and TR01 awards are all funded by the NIH Common Fund, with supplements from NIMH and other Institutes. Two other funding programs were developed via specific institutes. The EUREKA program (Exceptional Unconventional Research Enabling Knowledge Acceleration), developed originally in NIGMS but now supported by several institutes, funds exceptionally innovative research that, if successful, will have an unusually high impact. Funding includes direct costs of up to $800,000 over 4 years. Examples of projects NIMH has funded are described at Finally, NIMH’s BRAINS awards--Biobehavioral Research Awards for Innovative New Scientists—support the research programs and career development of outstanding scientists who are in the early, formative stages of their careers and who plan to make a long term commitment to research most relevant to NIMH.This award seeks to assist these individuals in launching an innovative clinical, translational, or basic research program that holds the potential to profoundly transform the understanding, diagnosis, treatment, or prevention of mental disorders. For information on the most recent awardees, see a previous blog,

The great Hungarian physiologist Albert Szent-Györgyi famously said that “discovery consists of seeing what everybody has seen and thinking what nobody has thought.” Breakthrough discoveries for NIMH will require visionary research across many areas of science from scientists who think differently. All of these mechanisms were designed to support this kind of research. A diverse group of investigators is making use of them with impressive results. We look forward to applications from many more scientists who are “thinking what nobody has thought” on the many critical questions NIMH endeavors to answer.