The President's BRAIN Initiative

At three pounds, 100 billion cells, 10,000 as many connections, the human brain makes Facebook look like child’s play of a network, not without reason: our brains are solely responsible for our every thought, emotion and action. The human brain is the most complicated machine in the known universe. It is fitting then, that President Obama announced this week that the state of our knowledge of brain function is in a sort of swamp despite tremendous progress in the past century, and it is time to pave our way out in an effort to solve how the brain functions.

The BRAIN Initiative seeks $100 million for the next fiscal year to fund new research into mapping connections between nerve cells, with the ultimate aim of curing monstrous diseases like Alzheimer’s, Parkinson’s, autism and PTSD. The cornerstone of the proposal, based on two idea-papers published by top neuroscientists in the last few months, in Science and Neuron, is to create new technologies capable of measuring the electrical activities of millions of brain cells at a time (the current state of the art is hundreds of cells).

The President hopes this sort of “big science” project will follow the Human Genome Project’s success in creating jobs and boosting the US economy, while unifying neuroscientists around the world in the pursuit of cures for major diseases (according to a Times article, a $600 billion annual worldwide toll for dementia care alone). While well-intentioned, the proposal is ripe with serious problems. Neuroscientists, like Prince Herbert, must be cautious.

One problem with the proposal - and a way in which it differs from previous Big Science projects - is that it’s not clear what victory would look like. With the Moon Shot and Human Genome Project, we had clear goals to work toward and knew exactly when those were achieved. On the other hand, how will we know when we’ve understood the brain? The Initiative’s aim to record from every neuron involved in a behavior doesn’t help its case - surely there are millions of possible behaviors one could study, with even more states in which the appropriate networks start the behavior, not to mention the multitude of ways a neural network can progress through learning. The proposal doesn’t clarify how such experiments could be set up or what information they would provide.

Interestingly, there is an effort already underway to map connections between brain cells to the resolution of the approximately 10,000 inputs per neuron in whole circuits or brains; the Connectome Project, led by Sebastian Seung, Jeff Lichtman and Winfried Denk, is quite controversial because its goal is to create static pictures of the connections rather than ever-evolving ones of electrical activity, but it is also very well defined and promises clear answers, much like the Human Genome Project did. One of the experiments proposed by the Connectome team, according to Jeff Lichtman, is to create diagrams of the circuit responsible for generating songbirds’ songs (a highly complex and well-defined learned behavior) before and after learning. Such data would be tremendously important for our understanding of how neurons organize themselves during learning to produce sequences of complex movements.

In addition to the vagueness of the BRAIN Initiative’s goals, its promise to cure diseases like Alzheimer’s reveals either a misunderstanding of how basic science works, or simply a dangerous exaggeration that will discredit neuroscientists in the public eye. If we fail to find cures in the next decade, will conservatives in Congress conclude that science just doesn’t work?

And while the proposed “mapping” of activity will provide great scientific insight into brain function, it won’t find cures horrible diseases such as Alzheimer’s because those are rooted in molecular and genetic failures rather than in neuronal electrical activity itself. Aberrant activity is a result, not a cause, of molecular and genetic problems; manipulating activity, such as Deep Brain Stimulation for Parkinson’s, is a temporary fix. The Initiativewill likely make the highest impact in cases of mechanical damage to the brain like stroke, where circuit function goes awry because dead neurons don’t make critical computations. In such cases, measuring activity in healthybrains will be enormously helpful to treatments.

Elements most critical to the Initiative’s success will not be those that define it, but those outside of it. The organizers must ensure that funding for BRAIN does not syphon money from existing projects or alternative and independent future proposals. Scientists must have the freedom to pursue their interests without having to follow the government’s vision.