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Inching Forward – An Initiative to Understand the Brain

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By: Varun Sethi, MD, Ph.D.

On April 2nd 2013, the twitter handle @BRAINinitiative re-tweeted a White House announcement that stated “Today we announce the next great American Project – the BRAIN initiative”. Since then, punctuated tweets have told the story of the evolution of this initiative to an audience of over 1400 followers. The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative was launched in 2013, as a 12 year long journey towards BRAIN 2025, identifying it as one of the major Grand Challenges for the 21st century and aiming to improve our understanding of the brain in action.

Neurological diseases, developmental and degenerative alike, are disabling, expensive and chronic conditions. The physical and economic burden of neurological diseases is only expected to increase with the growth of an increasingly aging population. At a time when the prevalence of neurological conditions is increasing across the spectrum, this initiative has been a catalyst to neurological research. The initiative aims to develop and apply new technologies, create maps of brain circuits, and improve the comprehension of behavior and cognition. With paradigm shifts in the practice of medicine, gravitating towards preventative and personalized medicine, this initiative allows neurologists and neuroscientists to evolve in their practice of care.

Co-ordination of the BRAIN Initiative at the National Institutes of Health (NIH) happens across ten NIH Institutes and Centers, with regular meetings to integrate strategic planning, management and support. Multi-council working groups ensure a coordinated and focused effort across NIH and amongst other Federal agencies. At the most recent meeting of the BRAIN multi-council working group on March 4, 2015, the proposed agenda included a discussion of BRAIN research supported by NIH, neuroethics, and presentations of BRAIN-related activities from the federal agencies involved.

The BRAIN Initiative is to neuroscience what the Human Genome Project was to genomics; this analogy has been stated often and sets a high bar, which the Initiative has continuously aimed to surpass. At its inception, this was announced as a $100 million grant. In 2014, the administration announced the growth of the BRAIN Initiative to include five participating federal agencies: the NIH, National Science Foundation (NSF), Defense Advance Research Projects Agency (DARPA), Food and Drug Administration (FDA), and Intelligence Advanced Research Progress Activity (IARPA). Members of the National Photonics Initiative, together with companies such as GE, Google, GlaxoSmithKline and Inscopix announced plans to leverage over $30 million in support of the BRAIN Initiative. Other agencies such as patient advocacy organizations, universities (e.g. University of Pittsburgh), and the Simons Foundation proposed a contribution of $240 million towards research efforts.

The FY2014 BRAIN investments at NIH included the first wave of BRAIN awards wherein $46 million was invested in 58 projects encompassing more than 100 investigators in 15 states and 3 countries. Data sharing and integration across projects was emphasized. The grants focused on transformative technologies and included amongst others classification of the myriad of cell types in the brain and creation of next generation human brain imaging technology to monitor circuit activity. In 2015, $65 million in funding was secured from the aforementioned five federal agencies. Five new funding announcements were announced, as also were two new opportunities, through the small business program on research.

In spite of the above, there is need for additional funding. Neuroscientists themselves insist that BRAIN be funded; Thomas Inel, director of NIMH had said in 2014, that his institute might be willing to redirect funds from other neuroscience projects so as to support BRAIN. In recent weeks, the BRAIN initiative was amongst the important agenda items discussed by members of the American Academy of Neurology (AAN) at the recent “Neurology on the Hill” event earlier this month. Inching forward towards its goal, President Obama’s FY2016 budget proposes increasing federal funding from about $200 million in FY2015 to more than $300 million in FY2016, for BRAIN. On March 3rd 2015, 156 members of the AAN met and urged members of the Congress to sign a letter of support for the BRAIN initiative at NIH, authored by Rep. Chaka Fattah (D-PA). The AAN members met with staff in 226 congressional offices and 80 members of the House and Senate. This highlights the interest and need for the continuous dedicated funding that is required to support the BRAIN initiative. A strong advocate for the initiative, former Indianapolis Colts player Ben Utecht spoke about his personal experience with traumatic brain injury and how increasing awareness through education is very important to change the standards of care.

The gradual evolution of the Initiative has been guided by analysis of the scientific and tool development goals from preceding years, together with incorporation of new goals towards the larger BRAIN 2025 objectives. The long term scientific vision of the NIH BRAIN initiative focuses on circuits and networks, calling for $4.5 billion in brain research funding over the next 12 years. Interim recommendations included ramping up support to $400 million per year by FY2018 and plateauing at $500 million per year by FY2021. Seven areas of research have been identified, all aiming to collectively map brain circuits and measure fluctuating patterns of electrical and chemical activity within those circuits, so as to elucidate the understanding of cognition and behavior.

The United States is not alone in prioritizing ‘brain health’. China had launched a similar, Brainnetome project. The European analogue, the Human Brain Project was launched with an ambitious 1.5 billion euros of funding over ten years, aiming to improve digital technologies, working together with neuroscientists. Often described as the Apollo program for neuroscience, BRAIN has steadily taken steps. However, is the inception of such programs enough? The need for a larger consensus in what the neuroscientists deem important together with a tangible improvement in health care are vital for the success of such an initiative. The recent discontent at the management of the Human Brain Project in Europe has called for a disbanding of the three member executive committee. This discontent stemmed from concerns about removing cognitive neuroscience as a priority from the initiative. Such trends highlight the need for a dynamic, continuous evaluation of such a vision and the need to be more inclusive. The step ladder, phased out approach towards funding, seems to have set the right trend but increased funding to meet goals remains a challenge and has not been without criticism. John Horgan had discussed the militarization of brain science and questioned the role of the Pentagon in funding the BRAIN. On the other extreme, Cori Bargmann, a co-chair of the advisory committee, provided economic rationale for the project stating, “To use numbers, the entire cost of the space program to put a man on the moon added up to about one six pack of beer for every person in America living at the time. And the entire cost of the Brain Initiative proposed here adds up, inflation corrected, to about one six pack of beer for each American over the entire 12 years of the program”. I don’t drink beer. But I feel the dilemma of rationalizing the ‘expense’ or ‘investment’. Depending on whether or not you can relate to a personal story of neurological disease, your opinion may vary, but the argument cannot be ignored. The proposed increase for funding FY2016 presents itself as a litmus test that, if successful, will validate the trajectory of the project and provide impetus for accelerated growth.

Alzheimer’s, Parkinson’s, multiple sclerosis, stroke – each is a devastating reality, with patient advocacy organizations and highly specialized neuroscientists, painstakingly looking for answers and therapies to improve, treat and someday cure these conditions. Is the larger vision of wire diagrams and maps of activity in the brain the correct end point? With a project such as this, can there be a clear end point? The brain–machine interface might be too far-fetched and futuristic. Nonetheless, in shifting from a disease-specific goal to a broader vision of understanding the circuitry of the brain, BRAIN encourages dialogue across disciplines and helps scientists overcome one of the largest obstacles of being highly specialized with a very unique skill set – ‘compartmentalization’. And yet, it cannot be understated that the possibility of a  breakthrough therapeutic option would be much more of an advertisement for the initiative, than a brain activity map. Areas of research that are not outlined as being of paramount importance are likely to be left behind, causing researchers in some areas to feel insecure and limited in the pursuit of science. The relatively myopic view of the Initiative is thought by many to be its biggest shortcoming.

“To keep the body in good health is a duty, otherwise we shall not be able to keep our mind strong and clear” Buddha. Roman poet Juvenal (Satire X 10.356-64) wrote “orandum est ut sit mens sana in corpore sano,” meaning “you should pray for a healthy mind in a healthy body”. So is a healthy mind as important or perhaps more important for a healthy qualitative life? Neurological disease is feared. Movement, perception and memory are equally important in ensuring we can lead healthy productive lives. However, is the global obsession to understand the brain justified? Neurological health is undoubtedly important, relevant and an increasing economic and physical burden. With a brain activity map, would we know the seat of the mind by 2025? Perhaps, perhaps not. It is, however, a good time to be a neuroscientist.

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Written by sciencepolicyforall

March 11, 2015 at 9:00 am

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