Here are some of the more important parts, but you really ought to read the entire article for yourselves.
Aaaannnnd moore's law strikes again, but luckily it was only a temporary setback.In 1999, Roger Tsien, a biologist at UC San Diego, was heeding Crick’s call for better ways to trigger neurons. When he read about Hegemann’s work with Chlamydomonas, he wondered: Could that photosensitivity somehow be imported into neural cells? To do that, it would be necessary to figure out which gene made the light-sensitive protein in the Chlamydomonas cell wall. Then the gene could be inserted into neurons so that, Tsien hoped, they too would fire in response to light.
Now, using light to make neurons fire wouldn’t be a huge deal; electricity could do that. But the exciting part was that a gene could be designed to affect only specific kinds of neurons. Scientists can mark a gene with a “promoter” — a cell-specific piece of DNA that controls whether a gene is used.
Here’s what they do: Insert the gene (plus promoter) into a group of viral particles and inject them into the brain. The viruses infect a cubic millimeter or two of tissue. That is to say, they insert the new gene into every neuron in that area, indiscriminately. But because of the promoter, the gene will only turn on in one type of neuron. All the other neurons will ignore it. Imagine you wanted only the lefty in an outfield to catch. How would you do that? Distribute left-handed gloves to all the players. The righties would just stand there, fidgeting and calling their agents. The lefty would spring into action. Just as the lefty is “tagged” by his ability to use the glove, a neuron is “tagged” by its ability to use the gene. Bye-bye side effects: Researchers would be able to stimulate one kind of neuron at a time.
It was a dazzling idea. Tsien wrote to Hegemann asking for the Chlamydomonas light-sensitivity gene. Hegemann wasn’t sure which one it was, so he sent two possibilities. Tsien and his graduate students duly inserted both into cultured neurons. But when exposed to light, the neurons did nothing at all. Tsien extracted two more genes from the algae and tried one of them, but that didn’t work either. “After three strikes, you have to admit that you’re out and try something else,” Tsien says. So he moved on to another line of research and put the fourth gene back into the lab refrigerator, unexamined.
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.
