By David Warmflash, MD | 7 May 2015
Genetic Literacy Project
Combining two technologies—optogenetics and neuroelectromechanical interfaces—researchers based in Switzerland and France have demonstrated a means for control gene expression through human thoughts. Triggered by three possible mindsets, each manifesting as a particular electroencephalographic (EEG) pattern, the system can turn on and off, and regulate a genetically engineered cyclic-di-GMO-dependent secondary messenger system.
The link between the two technologies is light, which activates a bacterial diguanylate cyclase (DGCL) that has been engineered to respond to near infrared (NIR) wavelengths. Within cultured cells inside an implant that the team tested in mice, the resulting molecular cascade leads to the synthesis of secreted alkaline phosphatase (SEAP), a human enzyme used frequently as a model for gene expression studies. The long-term expectation is that the approach will lead to novel mind-controlled drug delivery systems.
Mind control and gene control
Both technologies that the research has combined have been around for several years, progressing independently. Molecules that activate enzymes, affecting cascades that control gene expression, in response to light are part of nature. A well-known example is tanning, caused by the activation of melanin synthesis in skin cells called melanocytes in response to ultraviolet light (UV) from the Sun.
An even more sophisticated system regulates the production of chlorophyll in tree leaves, according to seasonal changes in the amount of light. This is what cause leaves to change color in autumn. In nature, there are many different molecules responding not only to light, but particular ranges of wavelengths. All light-activated gene-controlling molecules are either proteins, or made by protein enzymes, and thus are themselves products of genes. The term optogenetics refers to the harnessing of those genes to control molecular events in cells and tissues. In this case, an NIR-sensitive optogenetic system was chosen for combination EEG-controlled interfaces, because NIR is able to penetrate through skin and other tissue, without damaging it.
As for using the mind to control machines, particular EEG wave patterns are associated not only with seizures and the wake-sleep cycle, but also with different states of mind. Consequently, the last few years have seen progress on EEG computer interfaces being developed to enable people with spinal cord injuries to bypass the injury and use their minds to control robot implants that move the limbs.
— Nature Biotechnology (@NatureBiotech) February 18, 2021
Medical research aside, five years ago, the toy company Mattel came out with a game called Mindflex that works through an EEG in a headset, through which the player controls the speed of a fan to steer a ball through an obstacle course. Considering the Mindflex headset arrangement what inspired the authors of the new mind control gene expression study.
Using a Bluetooth type of headset linked to EEG sensors, human subjects in the Swiss-French study were trained to generate three types of electromagnetic patterns, corresponding to three mental states: biofeedback control, concentration, and meditation. The resulting signals were were harnessed to control on-off switching of NIR light with a wireless implant that also contained cells genetically engineered to respond to turn on the SEAP gene in response to the light. After being synthesized within the NIR-stimulated cells, SEAP is secreted from the implant, which the research team “implanted” into an in vitro setup (a cell culture, where SEAP concentration could be measured over time), and also subcutaneously in mice (in which SEAP concentrations could be measured in the bloodstream. In both the in vitro and the in vivo setup, the Bluetooth-wearing humans were able to turn the SEAP gene on and off.
While using a trio of thought patters to control gene expression for a protein in a laboratory setting may not sound like much more than a neat trick, the potential for medical applications is actually quite staggering. Consider, pain management for instance. EEG patterns connected with pain and other feelings could be utilized to stimulate genetic expression for enzymes involved in the synthesis of beta-endorphin. Even more imaginatively, the authors are thinking that, far in the future, brain wave patterns might also be able to control devices such as insulin pumps for diabetes, cochlear implants, various bionics, and even heart implants, all through optogenetic interfaces.
As with any very new biomedical technology, ethical issues will be raised as experts consider means through which the devices might be perverted for some negative application. Right now, it’s good material for a sci fi or spy thriller, and as the approach matures into one or more specific devices linking the delivery of gene products to the recipient’s state of mind, people will suggest potential horror applications by evil geniuses. But this happens often with new technologies, and at this point biomedical technology where almost anything in the wrong hands can produce horrors. For the moment, we should keep in mind that the new study represents a new direction for biomedicine. It’s a marriage of two powerful technologies, and at this point we should be inspired at the potential to improve the human condition.
Reprinted with permission from the author.
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Mysteries of the Brain: Brain-Computer Interface
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