Brain implants, drugs via blood-bubble, ingestible electronics - The Engineers, BBC World Service

Key Concepts:

• Brain-Computer Interfaces (BCI): Implantable devices that translate brain activity into commands for external devices.
• Targeted Drug Delivery: Delivering drugs specifically to the affected area to minimize side effects and maximize efficacy.
• Electroceuticals: Using electrical stimulation to modulate physiological processes, particularly via the gut-brain axis.
• Locked-in Syndrome: A condition where a person is aware but cannot move or communicate verbally due to paralysis.
• Stentrode: A specific type of BCI developed by Synchron, inserted via blood vessels.
• Microbubbles: Tiny gas-filled bubbles used as drug carriers, burst at the target site using ultrasound.
• Ghrelin: A hormone that promotes hunger.
• Biofilms: Communities of bacteria that are difficult to penetrate with antibiotics.
• HID (Human Interface Device): A Bluetooth profile for brain control.

1. Brain-Computer Interfaces (BCI) and Locked-in Syndrome (Tom Oxley):

• Tom Oxley's work is driven by the desire to bypass the "failed body" in conditions like locked-in syndrome, where the brain is active but motor control is lost due to stroke or other neurological damage.
• He recounts the experience of a young patient with locked-in syndrome, emphasizing the lack of effective treatments for major strokes and broken nervous systems.
• Synchron's BCI, Stentrode, is implanted via blood vessels, specifically the superior sagittal sinus, accessed through the jugular vein. This approach aims to minimize invasiveness compared to traditional brain surgery.
• The Stentrode detects electrical activity in the motor cortex, the brain's command center for movement. Algorithms are trained to recognize patterns associated with specific intentions (e.g., opening and closing a hand).
• These decoded intentions can then be used to control external devices, such as a cursor on a screen, via Bluetooth.
• Rodney, a patient, uses the latest Bluetooth profile developed with Apple, a new Human Interface Device (HID) for brain control. This allows for the development of features that are truly brain-derived, rather than tricking the computer into thinking the signals are coming from a keyboard or mouse.

2. Targeted Drug Delivery with Microbubbles (Eleanor Stride):

• Eleanor Stride focuses on improving drug delivery efficiency, as conventional methods (pills, injections) result in less than 1% of the drug reaching the target site, leading to side effects, especially with toxic drugs like chemotherapy.
• Her approach involves using microbubbles – tiny gas-filled bubbles (about 1/50th the width of a human hair) coated with a biocompatible material to encapsulate drugs.
• These bubbles travel through the bloodstream until ultrasound is focused on the target site, causing the bubbles to burst and release the drug locally.
• Stride's team faced the challenge of incorporating oxygen into the bubbles to combat hypoxia (oxygen deprivation) in tumors, which makes cancer cells resistant to treatment.
• Oxygen is a small, soluble molecule that easily escapes the bubbles. The solution involved modifying the bubble coating to be more gas-tight and partially substituting oxygen for the heavy, inert gas typically used in the bubbles. The heavy gas turned out to be a good solubilizer of oxygen, holding it all together.
• Human trials are planned for October, focusing on breast cancer patients undergoing surgery. The goal is to quantify drug delivery and cancer cell death.
• Beyond cancer, the technology is being explored for treating stroke (delivering clot-busting drugs) and chronic wounds (delivering antibiotics).

3. Electroceuticals and the Gut-Brain Axis (Khalil Ramadi):

• Khalil Ramadi's work explores the gut-brain axis, leveraging the gut's "little brain" (second largest number of neurons in the body) to influence brain function.
• The gut can function independently of the brain, making it an attractive target for therapeutic interventions without requiring invasive procedures.
• His electroceutical pill, "Flash," delivers electrical stimulation to the gut lining.
• Early experiments involved zapping pieces of stomach and measuring changes in gastrointestinal (GI) hormones. A robust increase in ghrelin (a hunger-promoting hormone) was observed.
• The pill is about the size of an omega-3 capsule and contains electrodes, a battery, and electronics to deliver micro-zaps. It stimulates for about 30 minutes and then passes through the digestive system.
• Potential applications include treating eating disorders, obesity, and potentially diabetes.

4. Ethical Considerations and Future Directions:

• Tom Oxley addresses ethical concerns related to BCIs, particularly privacy and the potential for dystopian scenarios as depicted in "Black Mirror."
• He argues that for individuals with paralysis, the loss of privacy is already a reality due to their dependence on others. BCIs could restore some of that lost autonomy.
• He acknowledges the risk of dependence on BCI technology and the need for long-term support, drawing parallels to the history of cardiac pacemakers and the challenges faced by companies providing cortical vision implants.
• The potential for BCIs to create a "different class of humans" with augmented abilities is raised, prompting questions about societal implications and potential discrimination.
• The potential for collaboration between the three engineers is discussed, highlighting the shared interest in solving unsolved problems and making an impact.
• The use of neural implants for more realistic VR gaming is suggested as a potential early application of the technology.
• The initial funding for BCI research came from the US Defense Advanced Research Projects Agency (DARPA), driven by the need to restore control of prosthetic limbs and understand post-traumatic stress from head injuries.

5. Questions from the Audience:

• A question about targeting bubbles at cells other than cancer cells is answered by Eleanor, who mentions stroke and chronic wounds as other potential applications.
• A question about the fate of unburst bubbles is answered by Eleanor, who explains that the gas leaks out, leaving a crumpled balloon that is processed by the liver.
• A question about the retrieval of electroceutical pills is answered by Khalil, who acknowledges the problem and mentions the parallel push towards making edible electronics.

6. Timeline and Availability:

• Eleanor estimates that her bubble technology could be available to the general public in about ten years.
• Khalil's invention is slightly less far along in development.

7. Conclusion:

The discussion highlights the innovative work of three engineers pushing the boundaries of biomedicine. Tom Oxley's brain-computer interfaces offer hope for restoring communication and control to individuals with paralysis. Eleanor Stride's targeted drug delivery system promises to minimize side effects and improve treatment efficacy. Khalil Ramadi's electroceutical pill explores the potential of the gut-brain axis for treating a range of conditions. While ethical considerations and challenges remain, these technologies hold significant promise for improving human health and well-being.