A Laser Light Show in the Brain
In 1992, Martin Chalfie made a spectacularly useful discovery, which I like to think of as perhaps the greatest use of cut-and-paste. Chalfie began with the fact that every gene has two parts: an encoding sequence that, using RNA as an intermediate, specifies a set of amino acids from which a cell can synthesize a protein, and a regulatory sequence that specifies, indirectly, when and where that protein should be built. By attaching the protein-coding end of a gene called GFP—a protein borrowed from a jellyfish that glows under a black light—to the regulatory region of other genes, Chalfie invented a new way in which scientists could harness nature’s toolkit to watch the actions of individual cells. It became possible to induce a particular class of neurons to shine under black light in order to ferret out what sort of circuit they might participate in.
In the summer of 2004, Ed Boyden and Karl Deisseroth, both working in the laboratory of Richard Tsien, took similar principles to an entirely new level, using the encoding sequence of a protein called ChR1, borrowed from unicellular green algae, which guides movement in response to light. In collaboration with Ernst Bamberg and Georg Nagel, Boyden and Deisseroth repurposed the gene into something new: a tool that could make individual neurons (or sets of neurons) fire on command. Boyden and Deisseroth then brought lasers, computers, and fibre optics into the mix, creating a way in which hundreds, or even thousands, of neurons could be manipulated in living, breathing animals with millisecond timing. (Previous techniques were less precise, and were largely limited to cells in a dish.) By shining lasers through optical fibres aimed at particular populations of neurons at specific times, a technique known as optogenetics, investigators can now effectively direct symphonies of light-induced neural activity inside the brain.