NEWS of what protagonists hope will be America’s next big science project continues to dribble out. A leak to the New York Times, published on February 17th, let the cat out of the bag, with a report that Barack Obama’s administration is thinking of sponsoring what will be known as the Brain Activity Map. And on March 7th several of those protagonists published a manifesto for the project in Science.The purpose of BAM is to change the scale at which the brain is understood. At the moment, neuroscience operates at two disconnected levels. The higher one, where the dimensions of features are measured in centimetres, has many techniques at its disposal, notably functional magnetic-resonance imaging (fMRI), which measures changes in tissues’ fuel consumption. This lets researchers see which bits of the brain are active in particular tasks–as long as those tasks can be performed by a person lying down inside a scanner.
At the other end of the scale, where features are measured in microns, lots of research has been done on how individual nerve cells work, how messages are sent from one to another, and how the connections between cells strengthen and weaken as memories are formed. Between these two, though, all is darkness. It is like trying to navigate America with an atlas that shows the states, the big cities and the main highways, and has a few street maps of local neighbourhoods, but displays nothing in between. BAM, if all goes well, will yield plans of entire towns and villages, and start to fill in the road network. It will also, to push the analogy to breaking point, let a user look at actual traffic flows on the roads in question, and even manipulate the road signs, in order to understand how particular communities work.
The mappers’ aim is to find out how nerve cells collaborate to process information. That means looking at the connections between hundreds, thousands and even millions of adjacent cells–and doing so, crucially, while those cells are still alive, rather than after they have been sliced and diced for microscopic examination.
This will require a new set of tools. And the guts of the BAM proposal are that the American taxpayer should provide those tools. It is thus no coincidence that the lead author of the paper, Paul Alivisatos, the director of the Lawrence Berkeley National Laboratory, is a materials scientist, not a neuroscientist. Dr Alivisatos and his 10 colleagues would like their new tools to be able to record, simultaneously, the activity of millions of nerve cells. Then, having done the recording, they would like a second toolkit that lets them manipulate each cell at will, to see what effect that has on the rest of the circuit. Finally, to handle the unprecedented amounts of data that the first and second steps will generate, they would like a new set of computing hardware and software.
A modest proposal, then. And one which is inducing polite scepticism from many neuroscientists who are not part of the charmed circle, and who fear their subject is about to be sacrificed to a juggernaut.
Such scepticism is reasonable. The third part of the project, the computer side, should be doable. That is just a question of pushing harder in a direction things are, in any case, going. How you would do the first two, though, is anybody’s guess–and Dr Alivisatos and his colleagues are pretty sketchy about the details.
Thinking big, thinking small
What ideas there are draw heavily on the nascent field of nanotechnology. This is Dr Alivisatos’s particular province, and also that of the Kavli Foundation, which exists “to advance fundamental research in the fields of astrophysics, nanoscience, neuroscience and theoretical physics”. A brain map would push two of those buttons, which accounts for the fact that five of the manifesto’s authors work for institutes sponsored by this foundation. But any successes that nanotechnology has enjoyed so far have been small beer compared with the devices that would be needed to interrogate nerve cells, record the results and transmit them back to base, let alone tell those nerve cells what to do.
The protagonists would, they say, build up slowly, using humbler creatures than human beings as experimental subjects to start with. This was the approach taken by the Human Genome Project, which began with bacteria and yeast, progressed to worms, flies and mice, and only then tackled people. But the analogy is not quite a fair one. When the genome project started, genomicists already had a basic understanding of how to go about it. That understanding was vastly refined and improved by the application of several billion dollars. But it was there from the beginning.
Going from existing methods of recording and manipulating cell activity, which rely on large electrodes, often connected to the outside world by physical wires, to the massively parallel, wireless system envisaged by Dr Alivisatos, is a different proposition. It may be possible. But it requires a leap of faith. The next few weeks will reveal whether that faith is shared by a cash-strapped president.
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