The brain in conscious control of genes—the idea sounds more outlandish than it should. After all, brain-computer interfaces, wireless power, and optogenetics already exist. It’s just that nobody thought to combine them before. Correcting this oversight, researchers at ETH Zurich assembled a system that has allowed humans to control gene expression by doing nothing more than adopting different mental states, or thinking different thoughts.
Thus far, the system has been used to control gene expression only in cell cultures and mice. But the system’s creators are hopeful that mind-controlled gene switches, which represent the integration of cybernetics and synthetic biology, could be refined to control gene expression in people.
For example, systems could be devised to combat neurological diseases such as chronic headaches, back pain, and epilepsy. After detecting specific brainwaves at an opportune time, the systems could instigate the creation of therapeutic agents exactly when needed.
The researchers described their work November 11 in the journal Nature Communications, in an article entitled, “Mind-controlled transgene expression by a wireless-powered optogenetic designer cell implant.”
“An electroencephalography (EEG)-based brain–computer interface (BCI) processing mental state-specific brain waves programs an inductively linked wireless-powered optogenetic implant containing designer cells engineered for near-infrared (NIR) light-adjustable expression of the human glycoprotein SEAP (secreted alkaline phosphatase),” wrote the authors. “The synthetic optogenetic signaling pathway interfacing the BCI with target gene expression consists of an engineered NIR light-activated bacterial diguanylate cyclase (DGCL) producing the orthogonal second messenger cyclic diguanosine monophosphate (c-di-GMP), which triggers the stimulator of interferon genes (STING)-dependent induction of synthetic interferon-β promoters.”
More succinctly, a headset sensor picked up a human volunteer’s brainwaves and wirelessly passed an EEG signal to a computer. The computer distinguished between signal types (“biofeedback control,” “concentration,” and “resting”) to determine whether to direct a field generator to produce an electromagnetic field, which induced a current in an implant. So far, so simple. More interesting is what then happened within the implant, which contained an LED lamp.
The LED lamp emitted light in the near-infrared range, illuminating a culture chamber containing genetically modified cells. When the near-infrared light illuminated the cells, they started to produce the desired protein.
This is the optogenetic part of the gene-switch system, which, admittedly, might seem a bit Rube Goldbergish if you’re technophobic. Of course, the ETH Zurich researchers, under the leadership of Martin Fussenegger, professor of biotechnology and bioengineering at the Department of Biosystems, were anything but. “Controlling genes in this way is completely new and is unique in its simplicity,” explained Prof. Fussenegger.
The light-sensitive optogenetic module that reacts to near-infrared light is a particular advancement. The light shines on a modified light-sensitive protein within the gene-modified cells and triggers an artificial signal cascade, resulting in the production of SEAP. Near-infrared light was used because it is generally not harmful to human cells, can penetrate deep into the tissue, and enables the function of the implant to be visually tracked.
“[Mind-genetic interfaces could] add a new dimension to electronic-mechanical implants such as heart and brain pacemakers, cochlear hearing aids, eye prostheses, insulin-releasing micropumps, and bionic extremities,” the authors of the Nature Communications article added. “Far into the future, patients may … learn to generate specific mental states [for pain relief or] locked-in syndrome programming or [placing] disease-related brain activities (for example, epilepsy, neurodegenerative disorders) under close-loop control, [via] therapeutic implants producing [as needed] doses of protein pharmaceuticals.”