Scientific American “Controlling the Brain with Light”

Neuroscience represents a sort of “last frontier” in biology: despite decades of research into the nervous systems of a diverse set of organisms, scientific understanding of how the web of neurons we call a brain creates complex emergent patterns of cognition and behavior remains limited. Part of the challenge faced by neuroscience has to do with complexity: our understanding of how complex networks function is rather poor in all contexts. But part of the problem is also technical, as the nervous system is hard to observe or manipulate at the fine scale on which it operates. And the means by which neurological manipulations have been performed is also an issue: even non-biologists can easily envision the field of neuroscience by conjuring an image of a rat, dog, or monkey with brutal electrodes planted in its skull. Noninvasive technologies like functional magnetic resonance imaging (fMRI) have moved the field beyond these days of electrodes, but fMRI can only yield rather large-scale, undifferentiated assessments of brain function.

An article in this month’s Scientific American (“Controlling the Brain with Light“) describes a novel approach to brain observation with the potential to eliminate both the crudeness and cruelty of older neuroscientific techniques. By combining the discovery of light-sensitive proteins (called opsins) in micro-organisms with existing recombinant DNA techniques, an emerging field dubbed “optogenetics” allows researchers to manipulate cell function at a very fine spatial and genetic scale through the use of different wavelengths and intensities of light. The article explains how: opsin genes are targeted to be inserted in front of a particular gene of interest, delivered via retrovirus into target cells, and then can be used to activate that protein in a living animal. While this technique could be used to study any cell type, the technology is most attractive to neuroscientists because it fits perfectly their need for specific manipulation of particular cells.

The article points out an interesting connection between optogenetics and the fields of ecology and evolution: while there is a fair amount of human ingenuity involved in this emerging technology, it also relies on the evolved ingenuity of ecological systems. Organisms developed opsins to solve their own problems (mostly having to do with appropriate response to an ever-changing local environment), and now researchers can harness this ‘design by nature’ to solve their own problems.

While this new technology is exciting and cool, it only eliminates one of the two major obstacles faced by the field of neuroscience. Having the ability to better observe and manipulate specific neurons will produce a lot of new data, but using that data to make sense of the complex networked systems we call ‘brains’ is another challenge altogether. Here, there is another lesson to be learned from ecologists: just because you have the ability to manipulate a complex system, that does not mean that you can meaningfully model how that system works. The excitement expressed in this article about the power of these new experimental techniques comes with a lot of promises about “reverse-engineering the mind”, and there is little mention of the theoretical challenge involved in fulfilling these promises. But at least neuroscience now has in its possession a more valuable means of poking the system to see how it responds.

Also, do not hold your breath for use of this technology in humans: while less invasive than electrode implants, optogenetics still requires a major intervention. It is hard to imagine any institutional review board approving the genetic engineering of human brains, although perhaps clinical trials aimed at treating incurable neurological diseases like Alzheimer’s disease might be deemed appropriate.