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Sun March 31, 2013
Science

Somewhere Over The Brainbow: The Journey To Map the Human Brain

Originally published on Sun March 31, 2013 9:55 pm

During the State of the Union, President Obama said the nation is about to embark on an ambitious project: to examine the human brain and create a road map to the trillions of connections that make it work.

"Every dollar we invested to map the human genome returned $140 to our economy — every dollar," the president said. "Today, our scientists are mapping the human brain to unlock the answers to Alzheimer's."

Details of the project have slowly been leaking out: $3 billion, 10 years of research and hundreds of scientists. The National Institutes of Health is calling it the Brain Activity Map.

Obama isn't the first to tout the benefits of a huge government science project. But can these projects really deliver? And what is mapping the human brain really going to get us?

Building A Brain Map

Much like the Human Genome Project a decade ago, scientists are hoping brain mapping will lead to new scientific advances and breakthroughs, and that perhaps it will even unlock the secrets of conditions such as Alzheimer's, schizophrenia and Parkinson's disease.

"With the brain, we're kind of at the same stage as we were in the early 1980s with the genome," says science writer Carl Zimmer.

Zimmer tells Laura Sullivan, host of weekends on All Things Considered, that there's no way to know what mapping the brain can do, but if mapping happens it's going to be both pricey and complicated.

"People have been studying the brain for centuries, and they've been mapping it, but the brain is just so complex that we barely understand it now," he says. "We have maybe 85 billion neurons in our heads, but we can only listen to maybe 1,000 at a time. [So] we're only getting a tiny picture of what the brain is doing."

There are several ways to map the brain, Zimmer says, one well-known example being an MRI. The resolution, however, is not nearly high enough for scientists to see all of the intricate wiring of the brain, where hundreds of thousands or even millions of neurons can fit in an area the size of a poppy seed.

"There are people who are trying to go down to that level," he says.

Some of this is already happening, albeit slowly, in labs around the world, Zimmer says. The problem is the efforts aren't coordinated.

"In the case of the Human Genome Project, the government said, 'We're going to coordinate all of this and we're going to get this genome sequenced,'" he says. "That's what the brain activity map people would like to do; coordinate all of this effort toward a common goal."

The next steps for the brain mapping project, Zimmer says, is simply to get a detailed plan going, and then get neuroscientists onboard. He says that debate should begin unfolding in the next few months.

Zimmer warns, however, that at first the project is likely to be underwhelming to the public, and Alzheimer's and other neurodegenerative diseases won't suddenly be cured. In all likelihood, scientists will study the brains of fruit flies and other creatures before moving on to the human brain.

"You have to walk before you can run," he says. "In order to develop the tools to map a human brain, you've got to start with much smaller brains made of the same basic kind of neurons. So look for big headlines about fruit flies the next couple of years."

The Human Genome Case Study

Completed a decade ago, the $3 billion human genome project, which mapped our DNA, was another massive science project undertaken by the government. In 2000, then-President Clinton said it would "revolutionize the diagnosis, prevention and treatment of most if not all human diseases."

That's a bit of a stretch even 10 years later, but for one man in particular it turned out not to be a stretch at all. When Clinton was giving that speech in 2000, oncologist Lukas Wartman had just entered medical school. During that time, he began having severe bone pain and high fevers.

"Finally, [I] dragged myself into the doctor," Wartman tells NPR's Sullivan. "So the next day, I had a bone marrow biopsy which showed the unthinkable, that I actually had leukemia."

Right away, Wartman began chemotherapy treatment. He responded well and went into remission. He finished medical school, but then the cancer came back.

"By this time, I was an oncologist myself, and kind of knew what was going on," he says.

Wartman took on intensive rounds of chemo and a stem cell replacement surgery. He was grateful when it worked and was ready to build a life. He focused on his research in the cancer lab and was thinking about the future.

Then one night, the fevers came back, as well as the exhaustion and he knew. He just couldn't face it.

"So this time, I did ignore it for a little while, and went to Spain, and went to my friend's wedding," he says. "The last thing I wanted to think about was the possibility of this coming back again, because I knew now that the odds of me surviving yet another relapse of this leukemia were just really poor."

Wartman joined a clinical trail, but it failed. There was nothing left, and it appeared to be a death sentence.

Then Wartman and his fellow researchers at the lab started thinking. The human genome project had figured out how to map healthy genes, so they decided they could use the same technology to map Wartman's healthy genes and compare them to Wartman's cancer genes.

When they compared them, they found a protein that the cancer relied on to survive. Wartman then scoured the database of every known drug on the market and found a drug made for something else entirely, that just so happens to kill the very protein his cancer needed to live.

Wartman started taking the drug on a Friday, and his blood counts were low. By Monday, his blood counts had perked up.

"The only word, and I don't necessarily mean this in a religious context, but this was almost like a miraculous response to this drug," he says.

Wartman and his colleagues had killed his cancer, and today he's completely healthy. Now, everyone else in the country with the form of leukemia that he had, and who is not responding to chemo, use the same drug.

"I probably wouldn't be alive today if it weren't for the human genome project," Wartman says. "Because I definitely benefited from the finances and the effort that the government put into a focused research question and it had very tangible benefits in my case."

Why Not Map The Brain?

Like the Human Genome Project, getting the science community onboard with a brain mapping project could be tough. Michael Eisen, a biologist at the University of California-Berkeley, has already started campaigning against it.

"The idea that science should be organized and funded in massive, centrally run projects that are organized by committees and bureaucrats in Washington rather than by individual scientists ... it just doesn't work," Eisen says.

Eisen says he agrees that government funding was necessary in collaborative science projects such as the moon landing or Human Genome Project. But, he says, this isn't one of those problems.

"If you listen to neuroscientists talk about this today, they don't even know what it means to understand the brain," he says. "This is not a moon shot."

Eisen says that in this instance, where creativity and innovation are needed, one of the worst things that the scientific community can do is put 500 biologists in a room to pursue a singular, consensus plan to get there.

Zimmer says there's another problem: How do you know when you're done mapping a brain?

"The problem is that while the genome was finite, the brain is really infinite," he says, "because not only does it have 86 billion neurons ... [and] 100 tillion connections, but those connections are changing all the time.

"It's very dynamic, and that's really what matters to us. ... So when do you know when you've finished mapping the brain?" he says. "You might never finish it."

But for Lukas Wartman, whose life was saved by gene mapping, it's far simpler. He says we have to take the leap, spend the money, cross our fingers and hope.

"I do understand that there's some resistance to it," Wartman says, "but at the same time, while it's not a sure bet, it's a bet that if it does pay off could really reap tremendous benefits for humanity.

"So I think as a society it would be great if we were willing to commit to supporting projects like that."

The details of the brain mapping project are expected to be released in the coming weeks in the president's budget proposal.

Copyright 2013 NPR. To see more, visit http://www.npr.org/.

Transcript

LAURA SULLIVAN, HOST:

It's WEEKENDS on ALL THINGS CONSIDERED from NPR News. I'm Laura Sullivan.

Coming up on the show, we remember Alcatraz through the eyes of one of the island's last inmates and last guards and a rarity in the magic business: a female magician.

But first, during the State of the Union, President Obama said the nation is about to embark on an ambitious project: to examine the human brain and create a road map to the trillions of connections that make it work.

PRESIDENT BARACK OBAMA: 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.

SULLIVAN: Details of the project have been slowly leaking out: $3 billion, 10 years, hundreds of scientists. The National Institutes of Health is calling it the Brain Activity Map. President Obama isn't the first to tout the benefits of a huge government science project. But can these projects really deliver? And what is mapping the human brain really going to get us?

That's our cover story today: big science, big project, big promises. Will mapping the brain be worth it?

(SOUNDBITE OF MUSIC)

SULLIVAN: Before diving into the human brain, let's look back a decade to the completion of another $3 billion government project: the Human Genome Project, which mapped our DNA. Here's President Clinton in 2000.

(SOUNDBITE OF ARCHIVED RECORDING)

PRESIDENT BILL CLINTON: It will revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases.

SULLIVAN: That is still a bit of a stretch even 10 years later. But for one man in particular, it turned out not to be a stretch at all.

DR. LUKAS WARTMAN: Hi. My name is Lukas Wartman, a physician-scientist, oncologist.

SULLIVAN: When President Clinton was giving his Human Genome Project speech, Wartman had just entered medical school, and he started to feel like something was wrong.

WARTMAN: Began having pretty severe bone pain and high fevers, and finally dragged myself into the doctor. And so the next day, I had a bone marrow biopsy, which showed kind of the unthinkable, that I had actually leukemia.

SULLIVAN: Right away, Lukas Wartman began chemotherapy treatment. He responded well, and he went into remission. He finished medical school, and then the cancer came back.

WARTMAN: By this time, I was an oncologist myself, so I kind of knew what was going on.

SULLIVAN: He took intensive rounds of chemo and a stem cell replacement surgery. He was grateful when it worked, and he was ready to build a life. He focused on his research in the cancer lab, and he was thinking about the future. And then one night, the fevers came back and the exhaustion, and he knew. He just couldn't face it.

WARTMAN: So this time, I did ignore it for a little while and kept all of my vacation plans, and went to Spain and went to my friend's wedding. And the last thing I wanted to think about was the possibility of this coming back again because the - I knew now that the odds of me surviving yet another relapse of this leukemia were just really, really poor.

SULLIVAN: He joined a clinical trial. It failed. There was nothing left. It was a death sentence. Except Wartman and his fellow researchers at the lab started thinking. The Human Genome Project had figured out how to map healthy genes. They decided that they could use that same technology to map Wartman's healthy genes and then compare them to Wartman's cancer genes.

When they did compare them, they found a protein that the cancer relied on to survive. Wartman scoured the database of every known drug on the market and found a drug made for something else entirely that just so happens to kill the very protein that his cancer needed to live.

WARTMAN: So I think that I started taking the drug on a Friday. And at this time, my blood counts were low, the leukemia wasn't very well controlled. But by Monday, when I had my blood testing again, my blood counts had perked up. The only word - and I don't necessarily mean this in, like, a religious context per se - but, I mean, this was almost like a miraculous response to this drug.

SULLIVAN: Now, everyone else in the country with the form of leukemia that he had and who aren't responding to chemo use that same drug.

WARTMAN: I probably wouldn't be alive today if it weren't for the Human Genome Project in reality because I definitely benefited from the finances and the effort that the government put into focused research question, and it had very tangible benefits in my particular case.

SULLIVAN: Thirty years ago, no one would have believed that what Wartman and his colleagues did with the technology from the Human Genome Project would have been possible. Today, a lot of scientists are hoping the same thing will be true of brain mapping that perhaps it will unlock the secrets of Alzheimer's and schizophrenia and Parkinson's.

CARL ZIMMER: With the brain, we're kind of at the same stage as we were in the early '80s with the genome.

SULLIVAN: Carl Zimmer is a science writer, and Zimmer says there's no way to know what mapping the brain can do, but if it happens, it's going to be both pricey and it's going to be complicated.

ZIMMER: People have been studying the brain for centuries, and they've been mapping it, but the brain is just so complex that we barely understand it now. I mean, we have maybe 85 billion neurons in our heads, but we can only listen to maybe 1,000, 1,200 of them at once. That's it. So we are really only getting this tiny, tiny little picture of what the brain is doing.

SULLIVAN: What does it mean to map the brain? Is this, like, a Google Map of the brain? Is this something visual that you can see on your computer?

ZIMMER: There are different ways to map the brain. So, you know, scientists, for example, right now map the brain with MRI. But the resolution only goes down to about a cubic millimeter, about the size of a poppy seed. And, you know, you can have hundreds of thousands or millions of neurons packed in there with all sorts of intricate wiring.

SULLIVAN: Inside that one poppy seed.

ZIMMER: Just inside that one, yeah. So if you really want to know the geography of the brain, you have to be able to zoom in down on that level. And so there are people who are trying to go down to that level. The problem is that it's slow. Even if you just get one millimeter of the brain is a huge effort. So that could take a long time.

SULLIVAN: And it's happening already. It's happening outside of the brain mapping project.

ZIMMER: Oh, yeah. This is happening in labs all over the world. The thing is that people aren't working together and saying, OK, who's going to handle this? Who's going to handle that? Who takes care of that? But in the case of the Human Genome Project, what happened was that the government said, OK, we're going to coordinate all of this, and we're going to, together, get this genome sequenced. That's what the brain activity map people would like to do, is to coordinate all this effort toward a common goal.

SULLIVAN: What can we look for in the coming weeks and months or coming years when it comes to this project?

ZIMMER: The first step is going to actually see the details of the plan. No one's seen the details of the plan yet. And then we're going to see neuroscientists getting on board or complaining about it and saying it's a bad idea. We're going to see that debate unfold in the next, I'd say, few months.

Now, if the brain activity map does go forward, then, you know, in the first few years, it's going to be pretty underwhelming for people who suddenly think that they're going to get cures for Alzheimer's because a lot of the focus is going to be on looking at the brain of, say, a fruit fly. And people might get very angry and say, the government's wasting money on fruit flies. But the fact is that you have to walk before you can run.

And in order to develop the tools to map a human brain, you got to start with much, much, much smaller brains made of the same basic kind of neurons, like the brains of flies. So look for big headlines about fruit flies the next couple of years.

SULLIVAN: Science writer Carl Zimmer.

Getting the science community on board with a brain mapping project could be tough. Michael Eisen of UC Berkeley is one biologist who has already started campaigning against it.

MICHAEL EISEN: The idea that science should be organized and funded in massive, centrally run projects that are organized by committees and bureaucrats in Washington rather than by individual scientists pursuing their own creative ideas and their own labs, as appealing as it may be to think about, you know, harnessing massive amounts of energy, all - getting everybody together in one place and getting us all on board with the same program, it just doesn't work.

SULLIVAN: Well, you know what I'm going to say here, right? I mean, the atomic bomb, putting a man on the moon and the Human Genome Project.

EISEN: There are times when we know exactly what we have to do: Build an atomic bomb, although I'm not sure that's everybody's idea of a good science project, or send an astronaut to the moon, or sequence the human genome, where it does take an effort of a lot of scientists coming together and working in a coordinated manner to solve it. But this is not one of those problems.

If you listen to neuroscientists talk about this today, they don't really even know what it means to understand the brain. This is not a moon shot, right? This is a perfect example of where biology is not rocket science. And there's plenty of evidence that when what's required is creativity and innovation and new insights into systems that the worst thing you can do is to put, you know, 500 scientists in a room and have them all pursue a consensus plan to get there.

SULLIVAN: Carl Zimmer says there's also another problem: How do you know when you're done mapping the brain?

ZIMMER: The problem is that while the genome was finite, the brain is really infinite, because not only does it have 86 billion neurons and not only does it have 100 trillion connections, but those connections are changing all the time. It's very dynamic, and that's actually what matters to us, is that dynamic nature of the brain. Our brains are changing moment to moment right now. So when do you know when you've finished mapping the brain? You might never finish it.

SULLIVAN: But for Lukas Wartman, whose life was saved by gene mapping, it's far simpler. He says we have to take the leap and spend the money, cross our fingers and hope.

WARTMAN: I do understand that there's, you know, resistance to it, but at the same time while it's not a sure bet, it's a bet that if it does pay off could really reap tremendous benefits for humanity. And so I think as a society, it would be great if we were willing to commit to supporting projects like that.

SULLIVAN: The details of the president's brain mapping project are expected to be released in the coming weeks in his budget proposal. Transcript provided by NPR, Copyright NPR.

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