How do you make a cyborg?
High on the list of requirements would be “a technology that allows targeted, fast control of precisely defined events in biological systems.” This technology now exists, although not exactly as it was envisioned on television in the ’70s. Today, the Six Million Dollar Man’s bionic enhancements would involve optogenetics—a technology based on a mix of micron-scale electronics, designer viruses, and a set of light-activated proteins taken from aquatic microorganisms.
Optogenetics was invented in 2005 when a group of scientists at Stanford University showed that they could control rat neurons using a light-activated protein transplanted from green algae. The killer feature of this algal protein is that, when activated by light, it generates an electrical current. In green algae, this light-sensing protein converts light energy into an electrical current as part of the process of harvesting energy from sunlight; transplanted into neurons, that same protein induces an electrical current that will trigger those neurons to fire. In other words, by simply expressing one new protein in neurons, scientists can control brain functions using beams of light.
Using optogenetics, scientists have shown that they can manipulate both memory and behavior in mice, and there is no reason why the same approach wouldn’t work in human brains.
Scientists and physicians have long been interested in making very specific sets of neurons fire in response to a stimulus. In the past, the way to artificially stimulate neurons was to use electrodes that directly apply an electrical current, but electrodes are like a sledge hammer: difficult to aim precisely, they indiscriminately stimulate any neurons in their vicinity, regardless of whether those neurons belong to the same class. With optogenetics, researchers get around this problem by making only very specific groups of neurons sensitive to light. By stimulating those specific groups with light, researchers can study what role those neurons play in learning, memory, and behavior, and they can manipulate neural circuits that are malfunctioning in disease.
Right now scientists are primarily using optogenetics in the lab, in research aimed at answering basic questions about how the brain works, and to explore possible treatments for neurological diseases like stroke, Huntington’s disease, and some forms of blindness. The U.S. Defense Department’s pie-in-the-sky research agency, DARPA, has also invested in optogenetics research focused on healing traumatic brain injuries.
More recently, optogenetics has moved into territory previously occupied by science fiction. Using optogenetics, scientists have shown that they can manipulate both memory and behavior in mice, and there is no reason why the same approach wouldn’t work in human brains. In July, a group of scientists at MIT reported that they successfully implanted false memories in optogenetically modified mice. They did this by placing the mice in a box and using light to activate a group of neurons during a fear stimulus (the mice were getting their feet electrically shocked). Later, the same group of neurons was activated naturally, in a completely different context (a new box). The mice acted as if they remembered getting shocked in this new context, even though the actual foot shocks were administered somewhere else. The point of this study was not to make a murine version of Inception, but rather to understand how memory is evoked by environment, a crucial issue in both addiction and post-traumatic stress disorder.
In the most dramatic demonstration of the potential of optogenetics, a team of scientists at the University of Illinois, together with my Washington University colleagues, created genuine mouse cyborgs. They built a micron-scale electronic device that could seamlessly interact with optogenetically modified neurons in a mouse’s brain.
To create a cyborg mouse, the researchers used engineered viruses to deliver light-activated proteins to the mouse’s neurological reward circuitry, and then injected a miniaturized electronic control device into the mouse’s brain. This device contained a small LED to activate the light-sensitive neurons, as well as various instruments for monitoring the brain’s response. They hooked the control device up to a wireless transmitter, which was mounted on the mouse’s head. The result was a mouse that, as the researchers reported, could engage in “wireless, optical self-stimulation.”
Optogenetics clearly ranks with other recent game-changing biological technologies like fluorescent proteins, RNA-based gene silencing, and inducible stem cells. While there are still some technological hurdles to overcome before optogenetics can be widely used to modify human biology (not to mention ethical hurdles as well), this technology is developing extremely quickly, and unlike some other promised biotechnologies, optogenetics may be useful much sooner than we expect.
