A lot of nerves. President Barack Obama is introduced by Francis Collins, director of the National Institutes of Health, at the BRAIN Initiative event in the East Room of the White House on 2 April.

Official White House Photo by Chuck Kennedy

A lot of nerves. President Barack Obama is introduced by Francis Collins, director of the National Institutes of Health, at the BRAIN Initiative event in the East Room of the White House on 2 April.

As White House Embraces BRAIN Initiative, Questions Linger

Emily is a staff writer at Science.

For neuroscientist Rafael Yuste, sitting in an ornate White House chamber yesterday listening to President Barack Obama heap praise—and some $100 million—on a brain-mapping initiative that he helped hatch was a "luminous" experience. "It felt like history," says the researcher, who works at Columbia University.

"There is this enormous mystery waiting to be unlocked," Obama told the East Room crowd packed with leaders of American neuroscience during a 12-minute paean to brain research (likely the most expansive yet delivered by an American president). By "giving scientists the tools they need to get a dynamic picture of the brain in action," he said, the new initiative will help scientists find a cure for complex brain processes such as traumatic brain injury and Parkinson's, and create jobs that "we haven't even dreamt up yet."

For all the lofty rhetoric, however, the White House didn't provide many details about how the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative will accomplish its mission. And the lack of detail is worrying not only BRAIN skeptics—who argue that it targets the wrong goal and could detract from other research efforts—but also even some staunch advocates such as Yuste. The way that the White House has packaged and plans to fund and coordinate the initiative, they say, is creating some unease.

"As the proposal stands, it's still awfully vague, so it's hard not to have some reservations," says biophysicist Jeremy Berg of the University of Pittsburgh in Pennsylvania, who is a former director of the National Institute of General Medical Sciences at the National Institutes of Health (NIH).

Several years ago, Yuste and other scientists originally pitched BRAIN to U.S. government officials as the Brain Activity Map, a 10-year, $3 billion effort to develop tools in nanotechnology, optogenetics, and synthetic biology that could measure "every spike from every neuron" in a neural circuit. In a 2012 paper in Neuron, based on meetings organized by the Oxnard, California-based Kavli Foundation, Yuste and colleagues laid out a plan to progress gradually from mapping the brain activity of simple model organisms such as the fruit fly to charting the brains of creatures that contain roughly 1 million neurons, such as the Etruscan shrew. Human applications were couched as the ultimate aim, but not an immediate goal.

Since the idea was adopted by the White House, however, it has evolved substantially. The plan that Obama unveiled yesterday calls for BRAIN to be funded by three federal agencies as well as private foundations. Officials say the president's fiscal year 2014 budget request, to be released on 10 April, will request approximately:

  • $40 million for NIH's Blueprint for Neuroscience Research, a project which spans 15 institutes and centers

  • $50 million for the Defense Advanced Research Projects Agency, for research that could improve treatment and diagnosis of combat-related conditions such as post-traumatic stress, brain injury, and memory loss

  • $20 million for the National Science Foundation (NSF), to support research into the development of nanoscale probes that can record the activity of neural networks; information processing technology that can handle the flood of data generated by BRAIN research; and better understanding of the neural representation of thoughts, emotions, actions, and memories

Four private groups—the Allen Institute for Brain Science, the Howard Hughes Medical Institute, the Kavli Foundation, and the Salk Institute for Biological Studies—say they will support the project by funding BRAIN related research at their institutions. (See this infographic for more details.)

The initiative will be steered by an NIH-backed working group of 15 neuroscientists, co-chaired by Cornelia Bargmann of Rockefeller University in New York City and William Newsome of Stanford University in Palo Alto, California.

Although that group will not release a detailed research spending plan until later this year, BRAIN is expected to put a greater emphasis on human applications than its original planners envisioned, says neuroscientist John Donoghue of Brown University, one of two researchers from the Kavli-led effort that has been named to the BRAIN steering committee (neuroscientist Terrence Sejnowski of the Salk Institute is the other).Human applications and animal research are now being thought of as "a parallel rather than a serial effort," he says. And NIH Director Francis Collins confirms that human applications will be of great interest: "We don't want to waste any time moving to science that has direct human applications," he said during a press teleconference yesterday.

That shift has created some worries. Yuste, for example, says that keeping human benefits in mind is important, but he wonders whether the project's original sharp focus on tool development may be diluted if the NIH advisory panel is dominated by traditional neuroscientists, rather than a more interdisciplinary mix of scientists including nanoscientists, optogeneticists, and synthetic biologists. "Neither Bargmann or Newsome are tool builders, so it's a worry that they are packing the committee with users, rather than tool builders," Yuste says, adding that he and some allies are asking NIH to add members to the panel. "We are asking for more technologists."

Just 2 months ago, Bargmann herself expressed skepticism about the project. "Based on my conversations, there is great concern in the neuroscience community that this sounds like a big central planning project that will take resources away from creative work," she wrote in a February e-mail to Science. "The project needs to make sense to those who care deeply about neurological disease and neuroscience, and we haven't seen the leaders in those areas involved yet." (ScienceInsider has not been able to reach Bargmann for comment since she was named co-chair to the working group.)

Although Pittsburgh's Berg was skeptical of the 10-year, $3 billion Brain Activity Map proposal, "now that it's been downsized somewhat and focused on technology development I feel much more comfortable with the project," he says. Based on his experience at NIH, Berg says that the emphasis on technology development is "a very good thing," because groups within the agency tend to struggle with developing new technologies" because they are "focused on what problem they're trying to solve rather than the technology development per se."

Allowing the system to be flexible and adapt over time is crucial, he says. The fact that Bargmann and Newsome are on the advisory group "adds a lot of comfort for me." While both are "spectacular contributors" to neuroscience, Berg says, they also have a broad view of how to administer both small and large science projects.

Like any big project, the success of BRAIN will ultimately depend on its leadership, Donoghue agrees: "There are a lot of people involved in this who have built independent careers running labs on their own. ... The question is whether they will all pull together in the same direction."

Still unclear is whether BRAIN's funding will siphon money from other research efforts and if the $100 million will be followed by further investments in coming years. "My understanding is that it's coming from new money" not previously allocated to neuroscience research, Donoghue says. Yuste's initial reaction to the figure was that it was "much too low" to accomplish the project's original goals.

But "that money has to be seen as something that can be built around, from which you can build forward," says Alan Leshner, CEO of AAAS (publisher of ScienceInsider). "At a time when funding is so tight across the government," White House support for neuroscience research is a "major opportunity," says Leshner, a former director of NIH's National Institute on Drug Abuse and acting director of the National Institute of Mental Health. "If the scientific community doesn't rise to the moment, shame on us."

Although there's no predicting whether Congress will approve the president's request, "there has historically been and there seems to be today bipartisan interest in this kind of innovative research," said White House press secretary Jay Carney yesterday during his daily briefing.

One top Republican leader in Congress has already expressed his support. "Mapping the human brain is exactly the type of research we should be funding," said Representative Eric Cantor (R-VA), the majority leader of the U.S. House of Representatives, in a statement. "It's great science."

(Obama, meanwhile, joked during his remarks that "presumably my life would be simpler" if scientists could map the brain. "It could explain all kinds of things that go on in Washington. We could prescribe something.")

Despite their concerns, many of the researchers who laid the foundation for BRAIN are simply happy to see at least part of their idea being realized. On the evening before the president's announcement, Yuste and more than a dozen other colleagues involved in the effort met for dinner in downtown Washington, D.C., for what they jokingly described as their "Last Supper." The feeling of accomplishment was "bittersweet," Yuste says. They were pleased that the Obama administration has embraced the project, he says, but now "it's out of our hands."

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