IF YOU want to build an atom bomb, land men on the Moon or work out the exact order of the 3 billion chemical “letters” in the DNA of the human genome, then Big Science, a large-scale project backed by a budget in the billions, will do it for you. But will it also do it for the brain, the understanding of which is, perhaps, the biggest scientific challenge of all? That is a question with particular salience now, as the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative gets going in earnest.

At the moment this endeavour, announced by Barack Obama in April 2013, is definitely small science—despite its proposed budget of $4.8 billion over the next decade. According to Rafael Yuste of Columbia University, who was one of its instigators, some 125 laboratories around America have signed up to dip their bread in the gravy, so that gravy is very thinly spread. This reflects the way neuroscience has been done until now, but Dr Yuste would like the future to be different. Genetics was similarly fragmented before the Human Genome Project began, but the bargain imposed on researchers by that project was that the process of sequencing would be centralised into a few laboratories, where it could be industrialised. This, as Dr Yuste and several of his co-sponsors of the original idea of BRAIN write this month in Neuron, is the model they think neuroscience should now adopt.

BRAIN’s specific remit, they point out, is to develop new technological approaches for the study of brains. For that purpose, they propose creating a handful of “brain observatories” which would design and build the equipment, and then make it available to teams of outside researchers, much as academic astronomers book (and pay for) time on large telescopes. In this way, the observatories could concentrate on the engineering: refining the equipment by experience and arriving at designs that might then be commercialised.

Manhattan-project transfer

Dr Yuste and his colleagues identify four types of technology that BRAIN needs. Three are improvements of existing methods. The fourth is largely terra incognita.

The first of the improvements is better computing power. Even the task of mapping a mouse brain will require 500 petabytes of data storage. A petabyte is 1m gigabytes. For comparison, finding the Higgs boson required about 200 petabytes. A human brain is vastly more complex than a mouse’s. It has around 86 billion neurons, compared with 71m in a mouse. And the wiring that links these neurons (cell protrusions called axons) is reckoned to be about 100,000km long.

The second improvement that is required of existing technology involves brain-scanning. At the moment, this has a resolution measured at best in millimetres, which is fine for its original purpose—clinical diagnosis—but useless for understanding how brains work at anything more than a superficial level. Higher-resolution scanners would permit researchers to look at small, functional groups of neurons, such as the neuronal columns of which brain cortexes are composed.

The third improvement Dr Yuste desires is to instruments that can study the connections between individual neurons, a field known as connectomics. At the moment, this can be done only to dead brains, and the tools usually employed are electron microscopes. As with many other fields, the more closely you want to look, the bigger the machines you need to do it. Dr Yuste and his colleagues would also like to overlay on the three-dimensional electron-micrographs of connectomics information from other machines, such as high-resolution fluorescent microscopes, which can detect the molecules present in particular parts of neurons.

That leads to the unknown land. This is the designing of nanoscale devices (ie, instruments whose dimensions are measured in billionths of a metre) which can do something approaching connectomics on living brains, by studying the activities of hundreds or thousands of interconnected neurons simultaneously. Only in this way can the true nature of the brain’s circuitry be understood.

Asking what these nanoscale devices will look like tends to generate a lot of handwaving involving words like “quantum dots” and “nanodiamonds”—both types of tiny crystal that might act as neuron-scale probes—but with little clear idea of how these crystal probes would be controlled and listened to. In their case, then, there is an argument for letting a thousand flowers bloom in laboratories large and small. But for the other devices on Dr Yuste’s shopping list, observatories do seem a good idea. And, as luck would have it, America has a network of institutions that might be pressed into service as such.

Critical mass

The National Laboratories, are, in many ways, Big Science personified. A lot of them started life as atomic-weapons establishments, so they know how to run large projects that go on for years. They also house five of the world’s ten fastest supercomputers. One, indeed, is ready and eager to go. Argonne, near Chicago, has been hiring out one of its instruments, an X-ray generator called the Advanced Photon Source, to biologists for several years. Last year, 2,000 of the 5,000 experiments conducted using it were biological, and Argonne has recently hired a neuroscientist specifically to run a project that will employ the photon source to X-ray mouse brains, with a view to mapping them at high resolution. It is also buying a top-of-the-range electron microscope, with which researchers will be able to zoom in on areas of the brain the photon source suggests are particularly interesting, and a flashy, new computer that will help analyse the results of all this. Argonne’s director, Peter Littlewood, thus hopes to create a model which other national laboratories thinking of developing brain observatories might follow.

Whether they do will depend a lot on the say-so of Ernest Moniz, America’s energy secretary, who is the labs’ collective supremo. He and Francis Collins, head of the country’s National Institutes of Health (and thus, in effect, BRAIN’s treasurer), have met several times to chew the matter over. Some in Congress think the energy department should be minding its own business. Dr Moniz, an astute politician, understands this. But he is also a scientist to his fingertips, for he was once head of the physics department at the Massachusetts Institute of Technology. That he will turn down the chance to be part of what may become the scientific adventure of the 21st century seems unlikely.