Every gene is controlled by a complex regulatory system that ensures when and how the information it contains is going to be utilised to create a specific product, such as a protein. This system is comprised of factors ranging from proteins like RNA polymerase (which is responsible for transcribing genetic information into RNA ,a more accessible format), to repressors which bind to key sites on the DNA and block RNA polymerase and subsequently the entire process of gene expression.
Naturally, the expression of genes is not constant, it is ultimately controlled by a series of environmental cues acting as switches, turning the gene on and off depending on necessity. In E. coli for example, the tryptophan operon is switched on only in the absence of tryptophan. Today, scientists through synthetic biology may produce a variety of switches. These switches may be controlled by cues ranging from light to biocomputers and may provide solutions to conditions such as diabetes and obesity.
At the same time, developments of cybernetics have resulted in the design of man-machine interfaces, allowing patients to remotely control prostheses using their brain waves. Already in 2006 such systems were developed, enabling tetraplegic patients to carry out tasks such as control of a television or even manipulation of a robotic arm.
Now imagine combining these advancements. That is exactly what a team of scientists has done in a recent paper published earlier this November. The scientists designed a “synthetic mind-controlled gene switch” which operates by translating brain activity into commands, executed by an implant, controlling the expression of a gene. The device consists of two main parts: An electroencephalography interphase (EEG) monitoring brain activity and an implant containing engineered cells that produce secreted alkalin phospatase (SEAP), a human glycoprotein.
The EEG records brain activity and distinguishes between different mental states such as meditation (a state of relaxation), concentration (a mental state resembling that of a person intensely gaming) and biofeedback (maintaining the observed meditation-meter value within a desired range, by self training). By studying differences in brain waves at different mental states, scientists set specific thresholds, over which the wirelessly connected implant might be activated.
The implant itself is optogenetic, using light to control a built-in cell culture. Of course mammalian cells are typically non-reactive to light (with the exception of retina cells) so designer cells with the ability to express the NIR light-activated bacterial diguanylate cyclase (DGCL) were created, using genes from the photosynthetic bacterium Rhodobacter sphaeroide. Generation of NIR causes a cascade of reactions which end up in the production of SEAP.
So activation of the implant produces NIR light, which stimulates the implant cells located in the cell chamber, causing a cascade of reactions, with SEAP as the final product. After SEAP reaches a concentration threshold, it enters the test subject’s blood stream through a semi permeable membrane. The implant is 23 mm and is slightly bigger than a Swiss franc coin and is powered continuously by an internally built power-receiving antenna.
At this early stage, the implants had to be inserted into mice, however the EEG headsets were controlled by humans. SEAP production in mice was controlled by human mental states and NIR production by the implant was visible through the mouse skin in real time . Removal of the implants resulted in a drop of SEAP in the test subjects.
Through the combination of cybernetics and optogenetics, activity of the brain, heart and even genes may be used to administer therapeutic medication. Such synthetic devices, enabling remote controlled gene expression may pave the path for new treatment options at the gene and cell level. Who knows, cybernetic pacemakers, hearing aids or even implanted insulin micropumps may soon be a reality.
Yet in a world where genes may be turned on and off at will, what other productive applications might this technology have, other than in a medical context?