At the Society for Neuroscience meeting earlier this month in San Diego, California, Science sat down with Geoffrey Ling, deputy director of the Defense Sciences Office at the Defense Advanced Research Projects Agency (DARPA), to discuss the agency’s plans for the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, a neuroscience research effort put forth by President Barack Obama earlier this year. So far, DARPA has released two calls for grant applications, with at least one more likely: The first, called SUBNETS (Systems-Based Neurotechnology for Emerging Therapies), asks researchers to develop novel, wireless devices, such as deep brain stimulators, that can cure neurological disorders such as posttraumatic stress (PTS), major depression, and chronic pain. The second, RAM (Restoring Active Memory), calls for a separate wireless device that repairs brain damage and restores memory loss. Below is an extended version of a Q&A that appears in the 29 November issue of Science.
Q: Why did DARPA get involved in the BRAIN project?
G.L.: It’s really focused on our injured warfighters, but it has a use for civilians who have stress disorders and civilians who also have memory disorders from dementia and the like. But at the end of the day, it is still meeting [President Obama’s] directive. Of all the things he could have chosen—global warming, alternative fuels—he chose this, so in my mind the neuroscience community should be as excited as all get-up.
Q: Why does SUBNETS focus on deep brain stimulation (DBS)?
G.L.: We’ve opened the possibility of using DBS but we haven’t exclusively said that. We’re challenging people to go after neuropsychiatric disorders like PTS [and] depression. We’re challenging the community to come up with something in 5 years that’s clinically feasible. DBS is an area that has really been traditionally underfunded, so we thought what the heck, let’s give it a go—in this new BRAIN Initiative the whole idea is to go after the things that there aren’t 400 R01 grants for—and let’s be bold, and boy, if it works, fabulous.
Q: For RAM, why did DARPA choose to focus on memory, and what kinds of memory do you hope to restore?
G.L.: All these [injured] guys and gals want to go back into the service. A lot of them can go back because we’ve got good prosthetic legs, and now we’ve got the prosthetic arm that’s really close to being FDA [Food and Drug Administration] approved. But the thing with brain-injured guys—the thing that really keeps them out—is they can’t remember how to do certain motor tasks like drive a car or operate machinery. Now I don’t know if we are at that point, but if we can fix hearts, and we can fix badly broken bones, why can’t we fix part of the brain? If you had to pick an area of the brain that you can fix, the memory area is the most obvious because motor-task memory is really pretty well-worked out in preclinical models. Declarative memory is very different than associative memory and emotional memory—that stuff, nobody even knows anything about it—but when you look at the work in rodents with memory motor tasks, you say ok, it’s still a big step but it’s rational.
Q: Does collaboration with the National Science Foundation (NSF) and NIH mean overlapping funding priorities?
G.L.: No, but we like to think they’re synergistic and complementary. There are scientists—you and I know them—who think big. They think, “I can do this if I only have the means to do it. Where am I going to get the means? Do I go to NIH, do I go to NSF? No.” DARPA is saying, “You want $20-30 million? We’ll give you $20-30 million.” What I’m hoping is that we’ll get two or three teams of really bold leaders who are doing this thing with different approaches. When you do that, you get a real big leader who now, instead of giving me 20% of time on a grant, is going to give 50% time, or 60% time because this is what they’ve lived their career for. You want these guys full of tension because if this is going to cure people, I’d be working on it night and day—I wouldn’t take a damn vacation, would you? What DARPA is saying is here’s your chance. Here’s the golden ring—who’s brave enough to step up and actually grab it?
Q: How will DARPA share its data? Will it be public?
G.L.: All the data that is gathered will be shared in an open forum—it’s contractually obligated. We have an RFI [request for information] out by Reza Ghanadan to do something called FABRIC. This is potentially the next Broad Agency Announcement—we don’t know yet because he hasn’t gotten it approved—but he’s in the planning stage. Reza is an electrical engineer who built a lot of Boeing’s functional architecture for their data management and also their data analysis. He is trying to create hardware and software architecture in which you can add in different layers of data and different kinds of data. That’s task area one. Task area two is the computational models that will be used across these scales and across these data sets.
Q: How will you protect proprietary information if all data is shared?
G.L.: There are different approaches—one is that when you go to publish you have to turn over the data at that time, which is reasonable. There’s another one where if you put some [data] in, you get some out. If you don’t put any data in, you have no access. And there’s a third way, our way, which is to use a contractual system. You make it legally binding and if someone says I don’t want to do it, then you say, “But you signed this contract.” End of story. In the grant system that’s a little harder, but that’s how we’re doing it.
Q: How should the neuroscience community gear up to meet the challenges DARPA and the wider BRAIN Initiative has set out?
G.L.: Now’s the time to say, where does their work have relevance and where is their work stymied? There are so many things that the government can spend its money on and there are so many other constituencies that are totally unrelated to the sciences which would argue, you’ve already put $5.5 billion of NIH money per year into this—why do you need more? That’s a reasonable question. We have to say to these people, “This is why this is a good thing.” We have to share with them what we’re trying to accomplish in a way that is meaningful to them and meaningful to us, and so I challenge the scientific community to help us do that. How does their important work fit into the grand scheme?
Q: How will DARPA address ethical issues involved in this research?
G.L.: I’m very proud of this. We started this even before we came out of the gate—I talked to Lisa Lee over at the president’s bioethics commission and Ellen Fox, head of ethics for Veterans Affairs, two people I highly respect. What Lisa’s group said, which I thought was very profound, was that the way this is going to work best is that as the programs unroll and we elucidate new information and new capabilities, the discussion has to be ongoing. You can’t a priori think of all the things that will come out so you have to have a process to look at what we call ELSI—ethical, legal, social implications.
We have a six-person ELSI panel—right now—we haven’t announced their names and I don’t want to give them up yet because I haven’t asked their permission—but they are incredibly prominent. They’ve already agreed to come on and on 26 November we’re convening our first meeting.