In 1979 Francis Crick, a famous scientist most noted for his role in the discovery of the structure of DNA, first suggested that progression of neuroscience was limited by our inability to independently control one type of cell while others were unaffected; he also suggested light may hold the answer.
It was around this same time that ecological studies were revealing the properties of light-sensitive proteins crucial to the survival of some algae and microbes. The unassuming microbes contained light-responsive proteins that controlled the flow of electrically charged molecules and regulated the function of these tiny forms of life.
Fast forward a few decades to 2005 and Karl Deisseroth's lab at Stanford University, where researchers were first able to successfully introduce these microbes to animal studies and control them precisely using light. This marks the birth of optogenetics: the combination of genetics and optics (light) to control specific cells, without disturbing wider processes in the tissue or organism. It’s an intricate yet beautifully simple technology that has transformed the work of scientists in over 800 laboratories around the world. Since 2005, optogenetics has been hailed as 'Method of Year' and 'Breakthrough of the Decade’ by major scientific journals and has rapidly become a prominent tool for neuroscientists spurring on developments in associated technologies to meet the demand of the growing market.
So how does it work? The natural diversity of microbes and algae offers geneticists an abundance of tools to create light-mediated triggers to apply to a range of studies. From the shallows of fresh water rivers around the world to the undernourished lakes in Egypt specialised gateway receptors have been discovered which characteristically responded distinctly differently to light. Broadly speaking there are two classes of light-sensitive proteins now used to investigate neuronal systems; ChR2 allows positive sodium molecules to pass in response to blue or red light and Halorhodopsin which regulates the flow of negative molecules in response to yellow light.
Just a few simple stages are required to successfully control cell function via optogenetics. First we begin with the presence of light-sensitive proteins either naturally occurring or genetically introduced to a system. Carefully timed pulses of light are then used to activate the receptors which respond to light, and subsequently control the cell’s response.
The final stage in optogenetic control is to record the effects produced by activating these gateways. This can be done in a number of ways from comparatively primitive recording of cell’s electrical potential to behavioural studies of free moving animals.
It is clear to see that optogenetics will continue to be an invaluable tool for improving our understanding of biology, nature and even our own thinking; it is also exciting to realise that optogenetics is still in its relative infancy and the control it offers for targeted small-scale events has limitless possibilities for future medical advances. Deisseroth himself reminds us “The lesson of optogenetics is that the old, the fragile and the rare-even cells from pond scum or from harsh Saharan salt lakes - can be crucial to comprehension of ourselves and our modern world.
Diesseroth, K. Nature Methods.’Optogenetics’ (2011).
Diesseroth, K. Scientific American ‘Controlling the Brain with Light’ (2010).