What Does Mapping The Brain Actually Mean?What Does Mapping The Brain Actually Mean?
July 9, 2014 1:09 p.m.
What Does Mapping The Brain Actually Mean?
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MAUREEN CAVANAUGH: This is KPBS Midday Edition, I am Maureen Cavanaugh. This year, the California legislature allocated $2 million for a basic science research project called Cal-BRAIN. Considering that the state is just emerging from years of deep budget cuts, the new funding is remarkable both for what it says about our economic recovery, and the potential of the brain mapping project. The funds are meant to complement the huge federal BRAIN initiative announced by President Obama last year. One man who has been pivotal in generating both projects is my guest, Ralph Greenspan, Director of UC San Diego Center for Brain Activity Mapping, and Associate Director of the Kavli Institute for the Brain and Mind. Welcome to the show.
RALPH GREENSPAN: Thank you very much.
MAUREEN CAVANAUGH: Remind us, if you would, about the national BRAIN initiative announced by the president. What is the objective?
RALPH GREENSPAN: That is the effort to foster new technologies to make it possible for us to see and understand much more about what the brain is doing. This is the same as what we are going to be trying to do in California, but with a particular California angle to it.
MAUREEN CAVANAUGH: I will ask you more about that in a minute. From what I understand, the initiative is a $100 million project, is it like the Human Genome Project?
RALPH GREENSPAN: It is like it in the sense that it is like the grand challenges that the government takes on. It has somewhat different problems to solve before it can really forage ahead. In the case of the genome project, they pretty much knew what the technology needed to be, and they could improve it enough to do the project. Here, we are in the position of having to develop new technologies, without knowing ahead of time which ones are going to be most effective.
MAUREEN CAVANAUGH: What does mapping the brain actually do?
RALPH GREENSPAN: This means that we want to be able to see in real time, and in great detail, the actual activity patterns of all of the nerve cells firing at communicating with each other at the same time. Which right now, we cannot see that.
MAUREEN CAVANAUGH: How much do we know now about how the brain works?
RALPH GREENSPAN: We know a great deal more than we used to and there is still a great deal more to find out. We have a very good idea of what some of the general mechanisms are for things like how we modify nerve cells during learning, and what are some of the neurochemicals and systems of the brain that are important for emotion, and so on. But what we have a poor picture of at the moment is how all of this works together at the modern scale. Many of the most important brain problems that exist in society, mental illness and many of the effects of brain injury and so on are very likely to be problems that occur at that broad level of interaction between regions.
MAUREEN CAVANAUGH: In other words, we know little pieces of how one hormone might work, or how a neuron is effected, but we do not know how the hormone or neuron work together in a specific moment in time to cause a certain event.
RALPH GREENSPAN: We know something about local circuitry within a small region where it is possible to make the measurements to see what the cells are doing. We cannot do that probably all at once. That is really what we feel these to be developed.
MAUREEN CAVANAUGH: Ralph, you were involved in writing a white paper proposal to the White House about funding a national brain mapping project. Did you at the time think that was a longshot?
RALPH GREENSPAN: Completely. We thought this was something that was worth a shot, it came about because the idea was hatched at a meeting that was organized by a parent organization of my Institute, the Kavli Foundation, and several other foundations. When the idea came up, there were about six of us, two neuroscientists, two experts, one of the people from the Kavli Foundation, and a veteran of the Human Genome Project. We felt this was really important, and it would be hard to get funding for. But the vice president of the Kavli Foundation said that she knew somebody named Tom Khalil in the White House Office of Science and Technology Policy. He once said to her, if you ever come across a great idea, let us know. She called him up, he asked for the white paper, and on a spur of the moment in about twelve hours we produced it.
MAUREEN CAVANAUGH: Before you actually got the official word that this was accepted, that the White House was going to move forward on this, you had a little hint that it might happen, tell us about that.
RALPH GREENSPAN: For a year and a half they told us that they were interested in it, and they may choose this is one of the grand challenges. After the reelection they kept saying it. But it was a doing the during the state of the union in 2013, that I was I was sitting in my darkened office and listening to my computer, when the president said that scientists are mapping the human brain and every dollar of research that went into the Human Genome Project returned $140 in economic activity. That was a passage that I put into our white paper, to try to get them hooked on an economic aspect of it.
MAUREEN CAVANAUGH: Somebody read it!
RALPH GREENSPAN: That is right.
MAUREEN CAVANAUGH: Why are the economic benefits of scientific research like this?
RALPH GREENSPAN: They are often not quite what you expect beforehand. They especially accrue to efforts to develop new technology. In the case of the Human Genome Project, there is a whole vast new industry of DNA sequencing and diagnostics, some of which was anticipated. But not to the same degree it now exists. Back in the 1970s when the war on cancer was mounted, that actually produce the techniques that became the biotechnology industry. When the moonshot was announced, that produced a whole raft of new engineering that has many broad applications. Technology investment in particular has enormous economic return, it turns out, because of the broad applications.
MAUREEN CAVANAUGH: And you speculate that the research could actually hatch a neurotechnology burst in businesses that would call themselves the neurotechnology industry?
RALPH GREENSPAN: Yes, and in California and San Diego in particular, they are very well poised to pull this off. It will be because of course our principal in the long term benefit that we see for this is for brain disorders of all sorts. But the technologies that get us there will have applications to many diseases, many things outside of biology, and there will be engineering applications as we understand how the brain works. We can design devices that will be more efficient. QUALCOMM is already investing a great deal of money in computer chips based on the strategies of the human brain, and the more that they know about the how the brain works, the better those will be.
MAUREEN CAVANAUGH: Is this why you pushed this complement to the national BRAIN initiative, the Cal-BRAIN project, because you see California as so central to this entire initiative?
RALPH GREENSPAN: Yes, a very high proportion of scientists who are best suited to do this work are in California. California has a much better culture of innovation and cooperation among scientists across institutions than anywhere else in the rest of the country. We are really well poised to do this, and as I said, San Diego is even better at this than the rest of the state.
MAUREEN CAVANAUGH: What role is UC San Diego going to be playing in this? I hear it will be a hub for this project, what does that mean?
RALPH GREENSPAN: We will have a leading role in bringing this to the attention of the legislature and seeing it through. Although discussions are still underway for exactly how this will be set up, part of the original proposal that we made to the legislature was for there to be two regional organizing centers that worked closely together, and UC San Diego would be one based on the fact that we are truly world leaders in neuroscience. UC Berkeley will be another because the Lawrence Berkeley Lab is a world leader in the development of these new technologies. A co-author on that proposal is the director of that laboratory, Paul Alivisatos. He is also one of the original six, who did the white paper to the White House.
MAUREEN CAVANAUGH: Basically, individual research teams will come to UC San Diego, said that this is what we want to do, this is the technology that we are trying to develop, and UC San Diego will make sure that everybody who is involved in that stays up to date and what is going on everywhere about that development?
RALPH GREENSPAN: That will be in part what we do, this is supposed to be a statewide grant program. It will require the assembly of team of scientists, some of whom may have not worked on anything related to the nervous system before and never thought about it. Part of what our role will be is to get these teams together as we have already been doing at UCSD for the last year, and as you say, keeping them abreast of what is going on, watching what they do, making sure that they can take the best advantage of one another to move this forward and converge on real technology for seeing what the brain does.
MAUREEN CAVANAUGH: You mentioned technology a number of times in discussing that this is the crucial element of moving this BRAIN initiative forward. There is a similar BRAIN initiative underway in the nations of the European Union. Many scientists have gone public with their criticism of the project, and the criticism seems to revolve around the fact that there is too much computer modeling and not enough small-scale bench work, when they are trying to figure out the series of the brain. How likely is it that our BRAIN initiative will encounter similar disputes?
RALPH GREENSPAN: We are not in line to have the same problem. Their proposed program is very heavily weighted towards making machine models based on what the brain does. I think part of those criticisms come from the idea that not enough is yet known about large-scale patterns in the brain to make those kinds of models. Since solving that problem is the number one goal, we feel as though we will be in fact providing the kind of foundational work that will make what they want to do possible.
MAUREEN CAVANAUGH: There were some scientists who opposed this project from the beginning, what was there opposition?
RALPH GREENSPAN: It was very interesting to see that emerge, it even came out at the very first meeting two years ago. I was chuckling when I heard it, as was the veteran of the genome project, because they were verbatim the same criticisms raised against the Human Genome Project twenty years ago. Since I was trained as a geneticist, I was one of the people objecting it, so I know those arguments very well. I could not agree more with the fact that I was wrong.
MAUREEN CAVANAUGH: What were the objections?
RALPH GREENSPAN: They are rather like what you had voiced as one of the European objections, not enough in the individual investigator initiated projects, objections to the idea of a large-scale project of any sort. And also criticism of the idea that we want to do something as comprehensive as this. Saying that you do not need to see all of it. If you look at the important parts, you will know what you need to know. We will answer those criticisms to say the way to know the important parts is when you can see how the whole system works together.
MAUREEN CAVANAUGH: And you can relate now to the results of the Human Genome Project to sort of enforce that argument, is that right?
RALPH GREENSPAN: Yes, there is nobody in the life sciences or medicine who is not benefiting either directly or indirectly from the outcomes of the Human Genome Project, whether with the sequences or the ability to generate them.
MAUREEN CAVANAUGH: The overall goal as I understand it of this project is basic research to find out how things work. There is also the objective of using that knowledge developed by the BRAIN initiative to help treat diseases and disorders that plague us and stemmed from the brain. Can you go through just a little bit what the hopes may be for the results achieved in this BRAIN initiative?
RALPH GREENSPAN: Yes. There is no question that brain disorders are one of the major burdens on society. They are enormously tragic for families and contending with them. At the moment, we can do for psychiatric disease is quite limited. The pharmaceutical industry is staging a wholesale retreat from trying to work on drugs that will actually help you get they've had so with little success. We think part they do not actually know what is wrong in those disorders. Similarly, with major burdens like Alzheimer's and Parkinson's disease, those are diseases where the sooner that we can see the subtle things that are going wrong in the brain, way before symptoms come along, the sooner it will be possible to use the current kinds of drugs under development to arrest degeneration. For conditions like dramatic brain injury, which is much more widespread than people realize in the general population as well as in the veteran population, we know almost nothing about that. We are really in the dark in trying to treat think that the stage. Similarly for autism and behavioral problems that cause serious societal burden, like addiction.
MAUREEN CAVANAUGH: That is the goal, at least in the clinical way, to find out the information that might give us the tools that we need to treat a variety of ailments. But you know, the Human Genome Project took ten years. How long do you expect it will take before we have break views in either mapping the brain or being able to use the knowledge that we acquire for specific reasons?
RALPH GREENSPAN: Fortunately, in the case of this project, there will be steps along the way that will already allow us to do some things without having to wait until we get to the end before any of that comes along. There will be enhancements to existing imaging technologies, enhancements to existing diagnostics, engineering outcomes as well that occur earlier. I think we will see benefits as we go along. Probably the most far reaching ones will be the ones that it takes the longest to get to. It is not the case that we simply have to hold our breath collectively until we get there.
MAUREEN CAVANAUGH: I want to congratulate you on the Cal-BRAIN project coming to UC San Diego. Thank you so much for speaking with us.
RALPH GREENSPAN: Thank you very much for giving me the opportunity.