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Their idea worked. The mice walked. In their paper, published in April 2009, they wrote that the “effects were not subtle; indeed, in nearly every case these severely parkinsonian animals were restored to behavior indistinguishable from normal.”
Over at MIT, Boyden was asking the obvious question: Would this work on people? But imagine saying to a patient, “We’re going to genetically alter your brain by injecting it with viruses that carry genes taken from pond scum, and then we’re going to insert light sources into your skull.” He was going to need some persuasive safety data first.
That same summer, Boyden and his assistants began working with rhesus monkeys, whose brains are relatively similar to humans’. He was looking to see whether the primates were harmed by the technique. They triggered the neurons of one particular monkey for several minutes every few weeks for nine months. In the end, the animal was just fine.
The next step was creating a device that didn’t require threading cables through the skull. One of Deisseroth’s colleagues designed a paddle about one-third the length of a popsicle stick. It has four LEDs: two blue ones to make neurons fire and two yellow ones to stop them. Attached to the paddle is a little box that provides power and instructions. The paddle is implanted on the surface of the brain, on top of the motor control area. The lights are bright enough to illuminate a fairly large volume of tissue, so the placement doesn’t have to be exact. The light-sensitizing genes are injected into the affected tissue beforehand. It’s a far easier surgery than deep brain electrical stimulation, and, if it works, a far more precise treatment. Researchers at Stanford are currently testing the device on primates. If all goes well, they will seek FDA approval for experiments in humans.
Treating Parkinson’s and other brain diseases could be just the beginning. Optogenetics has amazing potential, not just for sending information into the brain but also for extracting it. And it turns out that Tsien’s Nobel-winning work — the research he took up when he abandoned the hunt for channelrhodopsin — is the key to doing this. By injecting mice neurons with yet another gene, one that makes cells glow green when they fire, researchers are monitoring neural activity through the same fiber-optic cable that delivers the light. The cable becomes a lens. It makes it possible to “write” to an area of the brain and “read” from it at the same time: two-way traffic.
Why is two-way traffic a big deal? Existing neural technologies are strictly one-way. Motor implants let paralyzed people operate computers and physical objects but are incapable of giving feedback to the brain. They are output-only devices. Conversely, cochlear implants for the deaf are input-only. They send data to the auditory nerve but have no way of picking up the brain’s response to the ear to modulate sound.
No matter how good they get, one-way prostheses can’t close the loop. In theory, two-way optogenetic traffic could lead to human-machine fusions in which the brain truly interacts with the machine, rather than only giving or only accepting orders. It could be used, for instance, to let the brain send movement commands to a prosthetic arm; in return, the arm’s sensors would gather information and send it back. Blue and yellow LEDs would flash on and off inside genetically altered somatosensory regions of the cortex to give the user sensations of weight, temperature, and texture. The limb would feel like a real arm. Of course, this kind of cyborg technology is not exactly around the corner. But it has suddenly leapt from the realm of wild fantasy to concrete possibility.
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