The development of human-integrated cybernetics has faced two major challenges. First, humans can effectively interact with electronic devices without needing to implant them.
Almost all cybernetic human-machine interactions can be managed with just a touch, except in some medically essential cases.
Second, the human body’s biological systems at the cellular and genomic levels are far more advanced at sustaining life than any technology humans have created. Integrating current technology into the human body would actually be a downgrade in performance.
However, a new perspective on cybernetics is emerging, where technology plays a supportive role and human genetics drive the advancements.
Researchers at ETH Zürich in Switzerland have discovered a method to harness the power of genetic expression using innovative current technology.
In a study titled “An electrogenetic interface to program mammalian gene expression by direct current,” published in Nature Metabolism, the team introduces an electro-genetic interface called Direct Current Actuated Regulation Technology (DART).
This technology allows for time- and voltage-dependent transgene expression in human cells using direct current (DC) from batteries.
DART works by generating controlled levels of reactive oxygen species (ROS), which are produced during cellular respiration in mitochondria, peroxisomes, and NADPH oxidase in immune cells.
KEAP1, a crucial tumor and metastasis suppressor, is a natural ROS detector. It binds NRF2, a nuclear factor associated with antioxidative defenses, for degradation.
When ROS levels rise, KEAP1 releases NRF2, which then moves to the nucleus and activates antioxidant-response elements to coordinate antioxidant and anti-inflammatory responses.
In a proof-of-concept study using a diabetic mouse model, the researchers demonstrated that transdermal stimulation of engineered human cells with energized acupuncture needles through DART led to insulin release, restoring normal blood glucose levels.
The engineered cells were microencapsulated and implanted under the skin of the mice. Microencapsulation was used to shield the cells from the host’s immune system while allowing the free diffusion of nutrients and therapeutic proteins.
The implanted cells were then electrostimulated with acupuncture needles at various voltage levels and battery types, including AAA batteries, AA batteries, 9V blocks, and button cells.
A single daily electrostimulation of the implanted engineered cells at 4.5 V for 10 seconds triggered enough insulin production and release to restore normal blood sugar levels in the diabetic mice, comparable to long-acting insulin therapies that maintain stable blood-sugar levels for 24 hours.
DART is designed with safety in mind, using low-voltage DC sources (~4.5 V), minimal energy requirements (10 seconds, once per day), and acupuncture needle electrodes already approved by the World Health Organization and the US Food and Drug Administration.
In a potential consumer application, the most significant limitation might be having access to three AAA batteries with 10 seconds’ worth of charge left, or in an emergency, a cell phone charger.
While still in the early stages of development, DART technology could pave the way for wearable devices that enable direct gene-based therapies and metabolic interventions.
According to the study’s authors, “it should be straightforward to link DART control to the in situ production and dosing of a wide range of biopharmaceuticals.
We believe simple electrogenetic interfaces such as DART that functionally interconnect analog biological systems with digital electronic devices hold great promise for a variety of future gene and cell-based therapies, including closed-loop genetic interventions, real-time dosing, and global telemetric monitoring by medical staff or algorithms.”
