The front page of Monday's New York Times revealed the Obama Administration may soon seek billions of dollars from Congress to map the human brain, in an ambitious project many have claimed will do for neuroscience what the Human Genome Project has done for genetics.
Details probably won't emerge until March at the earliest, but it's a safe bet the Administration's plan will resemble a Brain Activity Map (aka "BAM") project outlined last year in the journal Neuron. BAM is an acronym you'll probably be hearing a lot in the weeks and months to come — so let's talk about what the BAM project is, what it isn't, and why it's raising both interest and eyebrows throughout the scientific community.
Your brain is vast on a cosmic scale. Billions upon billions of neurons communicate with one another via trillions of connections, giving rise to what amounts to a network of networks. Widely adopted (but by no means universally accepted) theories posit that these neural networks are the wellsprings of such complex processes as perception and action. Many neuroscientists believe that a detailed BAM could reveal valuable clues about these and other cognitive functions, and perhaps human consciousness, itself. Columbia University's Rafael Yuste is one of them.
Yuste is a co-author of a widely circulated BAM project proposal published last July in the journal Neuron, and one of the scientists whose advice the Obama Administration has sought in planning what the NYT characterized as a ten-year, multi-billion dollar undertaking. In an interview with io9, Yuste explained that the ultimate goal of the project is to create what he calls a functional map of the active human brain. "You could argue, in a very simplistic way, that everything that we are, our whole mental world, amounts to nothing more than neural circuits firing [in patterns] throughout the brain," Yuste said. By mapping circuit activity, Yuste thinks researchers can "discover patterns that are the physical representation and origin of mental states — of thoughts, for example, or memories."
Said map would amount to much more than what is often referred to as a "static" model — a wiring diagram that charts how neurons connect with one another. A "functional" model, Yuste emphasized, would go much further, by allowing researchers to see not just the connections between the tens of billions of neurons that comprise a human brain, but the individual action of every cell in a given neural circuit. George Church, a molecular geneticist at Harvard University, told io9 that it's like the difference between knowing the spatial distribution of a city's telephone wires and knowing where, when, and how those wires are transmitting messages. (An early architect and longtime ambassador of the Human Genome Project, Church has been tapped to work on the BAM project, and is a co-author on last year's white paper.)
Creating such a map will require nothing short of a technological revolution in the field of neuroscience. It is currently possible to insert electrodes into the brain that can both monitor and induce brain activity. But the resolution offered by these and less invasive techniques is poor. That means the first step toward a BAM will be to develop tools that can actually record the individual activity of every neuron in a brain circuit. The second step will be to create tools that can influence the activity of individual neurons.
In this sense, Yuste said, BAM "is essentially a technical development project," aimed at devising techniques that can both measure and stimulate neurons with exquisite spacial specificity. Development and implementation of these tools would, of course, begin on smaller organisms (think flies and mice) and specific brain regions, progressing toward the ultimate goal of plotting the real-time activity of the neurons and networks in an entire human brain.
To many, these tools would represent an enormous step forward for the field of neuroscience, producing therapeutic, financial, and intellectual fruit as rich and plentiful as The Human Genome Project. But more scientists are balking at the prospect of a multi-billion-dollar BAM project — and its comparisons to the HGP — than you might expect.
Grievances thus far — many of which have been aired and compiled in this piece over at the Atlantic — have centered on two concerns. The first is money.
Already strapped for cash, some neuroscientists are worried that an undertaking as massive as a BAM project could trigger a major reorganization of existing neuro funds, diverting precious research capital away from smaller projects ruled unsympathetic to the BAM cause. Other scientists fear the worst: a wholesale redistribution of all existing biological science funding (that means fields outside of neuroscience) to make room for BAM's multi-billion-dollar pricetag.
Though Yuste admitted he has little influence over which financial route Washington will take, he said he's pulling for the third, and by far most palatable, scenario: "The human genome was sequenced with new money, and BAM should not be funded with money reapportioned from other scientific enterprises."
"Our sincere hope," added Yuste, "is that this will be new money, new funding... not for us, but for the entire field" — with the additional proviso that "every single tool or technique [developed] will be immediately released for the entire neuroscience community."
Which brings us to the second major class of objection. Even in the unlikely event Washington does inject billions of new dollars into research, many feel the BAM project's conceptual aims remain far less clear than those of the Human Genome Project.
"I think the comparison between the Human Genome Project and BAM is completely inappropriate," Princeton genomicist Leonid Kruglyak told io9, "other than the fact that they're both big projects aimed at a large biological problem." In the case of the human genome, he said, the ultimate goal was extremely clear: "the three billion base pairs of the human genome, in order, defined."
"That's a pretty clear target to shoot at," he continued, "and I think, at least, many of the applications of that were very clear. Would it be valuable to be able to record the activity of a large number of individual neurons simultaneously? Absolutely. Would that solve how the brain works? I think that's a much bigger question."
Kruglyak said one of the main arguments for launching the Human Genome Project and conducting it in a centralized fashion was that researchers were already searching for disease genes and sequencing the genome in piecemeal. It was going to get done one way or the other, but it was going to happen in thousands of little bits at a time — highly inefficient from the standpoint of time and money. Centralizing the process through the Human Genome Project dramatically reduced costs while accelerating the mapping process toward a certain goal with definitive applications. "But I think even folks who are pushing BAM would agree that, even in a fifteen year time frame, they don't see any way of doing something similar for the human brain," said Kruglyak. "It would be a nice thing to do, but it's completely in the realm of science fiction at this point."
Church and Yuste have a far easier time drawing parallels between BAM and the Human Genome Project. They cite, for example, the potential for financial return. "I would argue that this will be more economically powerful than Human Genome Project," says Yuste. Churche echoed his colleague's sentiment."We learned from the HGP experience that technology should be done as early as possible," says Church, noting that he price of genome sequencing may have been brought down a million-fold, but only after the HGP project was over. "If you mix technology development and applications from the beginning, I think you wind up with a more cost effective, and relevant project. Those are things that we're going to do differently this time around."
"Humans are nothing but our brains," Yuste said of the potential applications for technology produced in pursuit of a map of human brain activity. "Our whole culture, our personality, our minds, are a result of activity in the brain." Church tempered Yuste's holistic response with specifics. He looks forward to new medical technologies like brain-computer interfaces for cochlear, epilepsy, spinal injury and retinal implants. These devices, he argues, only stand to improve, and at an enormous benefit to the economy. "We don't have to speculate on whether there's ever going to be a market for this stuff," he asserted. "There already is."