The messy quest to replace drugs with electricity

🌈 Abstract

The article discusses the development and challenges of "electroceuticals" - devices that use electrical stimulation to treat chronic diseases by manipulating the nervous system and immune system. It covers the initial promise and investment in this field, the technical hurdles encountered, and the emergence of alternative approaches to using electricity to directly influence cells and tissues beyond just the nervous system.

🙋 Q&A

[01] The Messy Quest to Replace Drugs with Electricity

1. What was the initial promise of "electroceuticals"?

• Electroceuticals were envisioned as a new class of implants that could replace drugs by directly controlling the nervous system and immune system to treat a wide range of chronic diseases.
• The key idea was to harness the electrical signaling of the peripheral nervous system, especially the vagus nerve, to modulate the immune system and reduce inflammation.

2. What were some of the early technical challenges faced in developing electroceuticals?

• Precisely targeting the correct nerve fibers within the vagus nerve bundle without hitting neighboring fibers and causing unwanted side effects.
• Lack of detailed anatomical maps of the peripheral nervous system to guide the targeting of specific nerves.
• Difficulty in avoiding the "on-target" and "off-target" effects associated with broad electrical stimulation of the vagus nerve.

3. How has the research focus evolved beyond just targeting the nervous system?

• Researchers have found that many non-neural cells, such as skin and kidney cells, can also respond to and be manipulated by electrical signals directly, not just through the nervous system.
• This has opened up new possibilities for electrical interventions beyond just targeting the nervous system, such as bioelectric bandages for wound healing and genetically engineered cells that can produce drugs in response to electrical stimulation.

4. What are some of the remaining challenges and open questions in the field of electroceuticals and bioelectric medicine?

• The optimal approach for targeting and stimulating the peripheral nervous system is still an open research question, with various strategies being explored.
• Demonstrating the long-term efficacy and safety of electroceutical devices in clinical trials remains a significant challenge.
• There is a need to overcome the "neurochauvinism" in the field and expand the focus beyond just the nervous system to other cellular and tissue-level electrical signaling.

[02] Other Cellular Responses to Electricity

1. What is the historical background of the discovery that non-neural cells can respond to electrical signals?

• In the late 19th century, the phenomenon of "galvanotaxis" was observed, where single-celled organisms would move in response to an electric field.
• However, this was largely forgotten until the 1970s and 1980s, when researchers rediscovered that a wide variety of cell types, not just neurons, could respond to electric fields.

2. What are some of the ways non-neural cells can respond to electrical signals?

• Galvanotaxis: the directed movement of cells in response to an electric field, which plays a role in wound healing.
• Changes in gene expression and signaling pathways in response to electric fields, which can influence cell identity and behavior.
• Generation of reactive oxygen species (ROS) in response to electric fields, which can be harnessed to control cellular processes.

3. How are researchers leveraging these non-neural electrical responses for medical applications?

• Development of "smart" bioelectric bandages that can monitor wound healing and adjust electrical stimulation to optimize the process.
• Engineering cells to produce therapeutic proteins in response to electrical stimulation, as demonstrated by the insulin-producing device.
• Exploring the use of electric fields to guide the regeneration of damaged nerves, such as in the optic nerve.

4. What are some of the challenges in translating these non-neural electrical effects into medical therapies?

• The complex and cell-type-specific nature of how cells respond to electric fields, requiring a deeper understanding of the underlying mechanisms.
• Overcoming the "neurochauvinism" in the field, where the focus has been primarily on the nervous system, and expanding the research and investment into these broader bioelectric approaches.
• Developing the appropriate experimental platforms and tools to study the collective, tissue-level responses to electric fields, rather than just single-cell or whole-animal studies.