June 2013

Reviewing the BRAIN Project

I was watching the State of the Union address with my family when I heard the following passage:

Now, if we want to make the best products, we also have to invest in the best ideas. Every dollar we invested to map the human genome returned $140 to our economy — every dollar. Today our scientists are mapping the human brain to unlock the answers to Alzheimer’s. They’re developing drugs to regenerate damaged organs; devising new material to make batteries 10 times more powerful. Now is not the time to gut these job-creating investments in science and innovation. Now is the time to reach a level of research and development not seen since the height of the Space Race. We need to make those investments.

I was delighted to hear President Obama acknowledge the tremendous potential impact of research.
 
Overnight, a friend pointed out a tweet sent by National Institutes of Health Director Francis S. Collins during the address:

@NIHDirector: Obama mentions the #NIH Brain Activity Map in #SOTU

I was puzzled and intrigued. NIH Brain Activity Map? A quick Internet search led to a 2012 paper in the journal Neuron. The authors of the paper proposed “launching a large-scale, international public effort, the Brain Activity Map Project, aimed at reconstructing the full record of neural activity across complete neural circuits.” This put the president’s remarks in a different context. Was the president referring to the tremendous progress that has been made in recent years on brain imaging? Or was he hinting at a new NIH project?
 
This point was clarified April 2 when Collins introduced President Obama in the East Room of the White House to announce a new proposal: the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) initiative. This proposal involves a first investment of approximately $100 million in fiscal 2014 from the NIH, the Defense Advanced Research Projects Agency and the National Science Foundation plus additional investments from private-sector partners. This announcement was followed by a public relations blitz, including an opinion piece by Collins and Microsoft co-founder and Allen Institute for Brain Science founder Paul G. Allen in the Wall Street Journal and an appearance by Collins on “The Colbert Report”:

 
Like many in the scientific community, I have been struggling to understand what is being proposed and how it relates to and affects ongoing NIH programs. In order to collect my thoughts, I turned to the format used for NIH grant-application reviews. Recall that the NIH is using a scoring system from 1 (best) to 9 (worst) in each of five criteria. My critique follows.

DESCRIPTION
(provided by applicants):

 
In science there are moments when prior discoveries, advances in technology and visionary leadership align to create the opportunity for a great leap. It happened in 1961, when President Kennedy called for a new era of space exploration, which took Americans to the moon. It happened again in 1990, when the Department of Energy and the National Institutes of Health transformed the future of biomedical research by launching the Human Genome Project.
 
The timing is perfect now for a federally coordinated effort to unlock the secrets of the brain, in line with President Obama’s call this month for an ambitious project to map the most complex organ in the known universe…
 
A new era of information technology allows us to build out super-data sets to track and organize these intercellular connections. With the aid of large-scale computer resources, we understand enough about the physics of the brain — in essence, a piece of highly excitable matter — to begin to simulate complete nervous systems…
 
Today we know that neurons fire, and we know that they are connected. We don’t know how they act in concert to govern behavior, the essential question in treating neurological disease and mental-health disorders. Most of all, we have a limited understanding of how the brain translates its rich sensory experiences into complex mental states and behaviors, all at the speed of thought.
 
Big problems demand big solutions. The human brain contains nearly 100 billion neurons of at least a thousand distinct varieties. Those nerve cells make at least 100 trillion connections. No single discovery, no one researcher, will be able to crack the brain’s code. The next generation of neuroscience breakthroughs will emerge from collaboration among a range of disciplines, from physics and biology to nanoscience, computer science and engineering. All hands must be on deck…
 
It is our view that tough fiscal times demand creative approaches and more innovation. As President Obama has noted, the Human Genome Project has returned $140 in economic growth and new industry for every government dollar invested. We are confident that the BRAIN initiative will pay comparable dividends over time and ultimately boost social productivity, reduce health-care costs and alleviate untold suffering. All humanity will benefit.
 

Critique 1: 

  • Significance: 1
  • Investigator(s): 3
  • Innovation: 5
  • Approach: 7
  • Environment: 5

Overall Impact:
The proposal presents a self-described bold attempt to understand the human brain. This is, of course, a challenge of the greatest significance. The greatest strength of the proposal, which should be embraced, is the appreciation by those in the highest positions that fundamental knowledge of structure, function and mechanism is necessary to tackle problems related to human disease and the development of desired applications. However, this enthusiasm is dampened by some implications that the approach will be centered on large-scale data collection without any clear discussion of the conceptual bases for data analysis and by the relatively opaque manner in which the proposal was generated. In addition, the tremendous financial challenges currently facing the American biomedical research enterprise require that the bar be set very high for such large-scale projects, given the clear, destructive consequences of redirecting funds away from investigator-initiated research programs.
 
1. Significance
Strengths 

  • • Understanding of the brain is one of the most fundamental challenges in human history.
  • • Such basic knowledge has tremendous potential to underpin understanding of the pathobiology of a range of neurological diseases that represent a substantial burden on individuals, families and society.
  • • Promoting collaborative approaches between a range of science and engineering disciplines spanning the basic-through-applied research continuum is essential for progress in many areas.

Weaknesses 

  • • The significance of large “super data-sets” in addressing problems such as the basis of brain function is unclear.
  • • The justification that the human genome project provided a 140-fold return on investment is not compelling. The HGP represents an important accomplishment with tremendous economic impact, but the factor of 140 is based on a study that undercounted the contributions of research not within the HGP budget and overcounted economic benefits. The applicants would be wise to view such economic studies with a critical approach similar to that they would use for other scientific studies. The expectation that any similar economic return will come from the present project is not justified.

 

2. Investigator(s)
Strengths 

  • • The neuroscience research community is very strong, with many good connections between biological, engineering and computational fields.
  • • An advisory board of outstanding neuroscience investigators has been assembled.

Weaknesses 

  • • Some of the spokespeople for the BRAIN initiative appear to have relatively little previous experience with neuroscience research.
  • • Some of the applicants have histories of promoting large-scale data collection projects without adequately recognizing the power of less directed and frequently more creative approaches.
  • • The engagement with leading investigators in the neuroscience community appears to have been relatively limited even when accounting for the early stage of this proposal.

3. Innovation
Strengths 

  • • Support for technology development and interdisciplinary research has the potential to develop innovative tools and approaches.

Weaknesses 

  • • The proposal does not recognize adequately the range of ongoing activities related to mapping brain connections and developing tools for neuroscience research and does not articulate how it is different from them.

4. Approach
Strengths 

  • • Coordination of activities between research programs at different agencies has the potential to enhance brain research.

Weaknesses 

  • • The approach is unclear, particularly with regard to the relationships between brain-activity mapping and other goals.
  • • The need for a large-scale, federally coordinated program rather than appropriately supported, investigator-initiated alternatives is not adequately justified.
  • • If the goal is to “crack the brain’s code,” the applicants would be wise to recall that “genetic code” was cracked not through large-scale data collection but rather through carefully conceived and incisive experiments designed and executed by individual investigators and small collaborative groups.
  • • The comparison with the program to put a man on the moon and the HGP is not apt, as those programs’ ultimate goals were relatively unambiguous. In contrast, it is unclear how one would judge if an understanding of the brain or a brain-activity map had been achieved.
  • • The types of coordination of activities from different agencies in both new and ongoing activities are not described adequately.

 

 

5. Environment
Strengths 

  • • There is a strong and vibrant neuroscience research community, including a range of interdisciplinary centers and programs that are well suited to contribute to this program.

Weaknesses 

  • • Unprecedented financial challenges are gripping the American scientific community, and the laboratories of many investigators at both early and mid-career stages are downsizing or are in danger of closing down. In this context, it appears that directing resources away from the investigator-initiated grants programs has the potential to inflict additional damage and exacerbate the inefficiencies associated with investing time and financial resources in developing effective and productive laboratories only to underinvest in their continuing activities.

Budget and Period of Support: There is little clarity about whether this program is intended to be supported with additional funds or by redirection or recounting funds that already are allocated to brain research. This is true both for the proposed federal support and for the listed contributions from nonfederal agencies. The intended duration of the program is unclear.
 
This completes my initial review. I hope that others in the scientific community will contribute their perspectives so that we can have an appropriate discussion of how the BRAIN initiative moves forward.

Photo of Jeremy BergJeremy Berg (jberg@pitt.edu) is the associate senior vice-chancellor for science strategy and planning in the health sciences and a professor in the computational and systems biology department at the University of Pittsburgh.

 

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2 Comments

  • FACTUAL ERRORS OF UNQUALIFIED BIASED REVIEWERS KILLED MY GRANT!!11!! I APPEAL!!!!11!!

  • Thumbs up! As Arthur Kornberg loved to remind people, there is no more efficient way of spending NIH $$ than through the untargeted R01 pool. Thanks, Jeremy, for carrying the banner so elegantly!

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