ARE we ever going to figure out how the brain works?

After decades of research, diseases like schizophrenia and Alzheimer’s still resist treatment. Despite countless investigations into serotonin and other neurotransmitters, there is still no method to cure clinical depression. And for all the excitement about brain-imaging techniques, the limitations of fMRI studies are, as evidenced by popular books like “Brainwashed” and “Neuromania,” by now well known. In spite of the many remarkable advances in neuroscience, you might get the sinking feeling that we are not always going about brain science in the best possible way.

This feeling was given prominent public expression on Monday, when hundreds of neuroscientists from all over the world issued an indignant open letter to the European Commission, which is funding the Human Brain Project, an approximately $1.6 billion effort that aims to build a complete computer simulation of the human brain. The letter charges that the project is “overly narrow” in approach and not “well conceived.” While no neuroscientist doubts that a faithful-to-life brain simulation would ultimately be tremendously useful, some have called the project “radically premature.” The controversy serves as a reminder that we scientists are not only far from a comprehensive explanation of how the brain works; we’re also not even in agreement about the best way to study it, or what questions we should be asking.

The European Commission, like the Obama administration, which is promoting a large-scale research enterprise called the Brain Initiative, is investing heavily in neuroscience, and rightly so. (A set of new tools such as optogenetics, which allows neuroscientists to control the activity of individual neurons, gives considerable reason for optimism.) But neither project has grappled sufficiently with a critical question that is too often ignored in the field: What would a good theory of the brain actually look like?

Different kinds of sciences call for different kinds of theories. Physicists, for example, are searching for a “grand unified theory” that integrates gravity, electromagnetism and the strong and weak nuclear forces into a neat package of equations. Whether or not they will get there, they have made considerable progress, in part because they know what they are looking for.