The Peter Attia Drive – Episode #363

"A new frontier in neurosurgery: restoring brain function with brain-computer interfaces, advancing glioblastoma care, and new hope for devastating brain diseases"
Guest: Edward Chang, M.D. (Chair of Neurosurgery, UCSF)
Date: September 8, 2025

Overview of the Episode

In this episode, Dr. Peter Attia sits down with Dr. Edward Chang, a pioneering neurosurgeon and neuroscientist, to explore the profound advances in modern neurosurgery. The discussion traverses the historical evolution of brain surgery, the latest breakthroughs in the treatment of brain tumors like glioblastoma, and the astonishing developments in brain-computer interfaces (BCIs) that are restoring function for patients with paralysis and lost speech. Dr. Chang shares both the technical and philosophical challenges of the field, the multi-disciplinary nature of current innovations, and his vision for making currently devastating brain diseases chronic or manageable by 2030 and beyond.

Key Discussion Points and Insights

1. Neurosurgery: Historical Context and Evolution

• Early Foundations and Trailblazers
  • The field began in earnest in the late 19th and early 20th century (Harvey Cushing, Wilder Penfield) with a focus on tumors, vascular disease, the spine, and later, functional interventions.
  • Quote:
    "Harvey Cushing was just the starting point of modern neurosurgery. Then there’s Wilder Penfield... really the beginning of what we’d call, consider modern epilepsy surgery." (Dr. Chang, 05:12)
• Surgical Innovation and Minimally Invasive Trends
  • Many procedures (craniotomy) remain similar to a century ago in their essentials, but techniques have radically evolved: laser ablation, focused ultrasound, and especially catheter-based vascular procedures (e.g. for stroke).
  • Quote:
    "The force of evolution [in surgery] is guiding us towards things that are more minimally invasive, less collateral damage to get to the targets and getting people back to life sooner." (Dr. Chang, 10:17)

2. Understanding and Tackling Glioblastoma Multiforme (GBM)

• Nature of GBM
  • GBM is an aggressive, usually fatal brain cancer affecting all ages, with high heterogeneity and resistance to traditional therapies.
  • Surgery can prolong survival but is almost never curative due to microscopic infiltrative disease.
• Recent Advances
  • Genetic profiling and immune-based strategies are paving the way for more personalized treatments.
  • Disrupting the blood-brain barrier with focused ultrasound for targeted drug delivery is under active investigation.
  • Quote:
    "We’re now moving from an era where we use a visualization of the histology now to this molecular profiling, which is more mechanistic." (Dr. Chang, 12:01)
• Future Hopes
  • Ideally, turning GBM into a chronic, manageable disease rather than an immediate death sentence.

3. Awake Brain Surgery and Brain Mapping

• Why Brain Surgery Can Be Performed Awake
  • The brain itself does not have pain receptors; pain-control focuses on scalp and dura.
  • Awake surgery allows real-time mapping of language and motor areas to avoid post-op deficits.
  • Quote:
    "The brain itself, which is processing that information in the body, actually doesn’t have those receptors itself." (Dr. Chang, 23:03)
• Split-Second Decisions and Brain Mapping
  • Surgeons must weigh the benefit of more aggressive tumor resection against the risk of functional loss, aided by intraoperative cortical mapping.
  • The concept of "real estate" is crucial: some brain regions are redundant, others are absolutely critical.
  • Quote:
    "There is some really expensive real estate in there, and there’s also some cheaper real estate." (Dr. Chang, 28:05)

4. Plasticity and Redundancy of Brain Function

• Reorganization After Injury or Slow-Growing Lesions
  • Brain can shift function laterally (e.g., from one frontal lobe to another) over time, demonstrating "synaptic plasticity."
  • Quote:
    "What happens is some neurons get lost over time and then others will compensate in terms of that function." (Dr. Chang, 30:11)
• Corpus Callosotomy and Consciousness
  • Severing the corpus callosum for untreatable epilepsy prevents seizure generalization but can cause dissociation syndromes—a powerful demonstration of lateralized function.

5. Brain-Computer Interfaces (BCIs): Restoring Communication

• Origins and Scope
  • BCIs record neural or electrical brain signals and use machine learning to infer intended speech, motor movements, or device control.
  • Crucial for patients with locked-in syndrome, ALS, or severe stroke.
  • Quote:
    "Replacing function has never really been possible until very recently." (Dr. Chang, 40:26)
• Case Study: “Ann” and Speech Restoration (2023–2024)
  • A woman, paralyzed and unable to speak for 18 years after brainstem stroke, received an ECoG array (253 electrodes, credit card-sized) on her cortex.
  • An AI model was trained to recognize her intended speech, translating attempted speech into text and then synthesized speech at up to 80 words per minute (normal conversation ~150 wpm).
  • Quote:
    "[Ann] was one of our participants… We could essentially reconstruct her words from her neural activity—even after not speaking for 18 years." (Dr. Chang, 72:58)
• Technical Approaches
  • ECoG (electrocorticography): electrodes placed on the brain’s surface; provides ~1,000x the resolution of scalp EEG, with less immune response compared to penetrating electrodes.
  • Moving rapidly toward fully implantable, wireless systems to eliminate infection risks.
  • Quote:
    "We’re seeing a convergence of what’s possible with electrical engineering… high bandwidth wireless… sensors on a substrate thinner than paper." (Dr. Chang, 53:27)
• Limitations and Future Steps
  • Hardware is already advanced; challenges now are in engineering optimization, scaling, and reducing invasiveness.
  • The future will include combining BCI with functional electrical stimulation (FES) to not only communicate but restore movement or breathing.

6. The Interdisciplinary Nature and Future of Neuroengineering

• Beyond Medication to Engineering Solutions
  • Many neurodegenerative disorders have modest responses to drugs; engineering approaches that directly restore or bypass lost function are now feasible.
  • Collaboration needed among neuroscientists, engineers (electrical, materials, mechanical), biologists, and clinicians.
• Biological Computing—The Next Frontier
  • Potential for engineered biological interfaces—organoids, synthetic cells—to someday replace or supplement electronic BCIs.
  • Quote:
    "Biology has solved a lot of these scaling problems. Cells that have the same genetic programming… end up having different identity, different purpose." (Dr. Chang, 92:23)
• Ethical and Societal Implications
  • As technology shifts from restoring deficits to possible enhancement, profound ethical debates will arise.

7. Next 10–15 Years: Aspirations and Predictions

• For 2030 & 2040:
  • Make BCIs a standard, widely available solution for speech, mobility, and possibly more functions in patients with ALS, stroke, spinal cord injury, and other conditions.
  • Glioblastoma managed as a chronic disease through molecularly targeted and immunological approaches.
  • Parkinson’s disease cell-based (possibly synthetic) transplants for focal neuronal loss.
  • Early detection and intervention in cognitive disease (Alzheimer’s, etc.) might offer better outcomes, but total reversal is still challenging.
  • Quote:
    "Let’s get a couple of these [solutions] across the finish line so that they’re actually out in the world helping people." (Dr. Chang, 95:11)
• Minimally Invasive Everything
  • The ongoing shift from open brain surgery to less invasive, safer, and scalable approaches.

8. History, Perspective, and Inspiration for Medicine

• The Legacy of Cushing and Penfield
  • Neural engineering, BCIs, and brain mapping would be unimaginable to early pioneers.
• Call for a New Generation
  • Dr. Attia urges young innovators to enter medicine, emphasizing the extraordinary impact possible at the intersection of neuroscience and technology.
  • Quote:
    "There is really an opportunity to bend the arc of civilization by choosing a career in medicine. And what you’re doing, Eddie, is really on the forefront of that, especially the way it combines all disciplines of science, medicine, and technology." (Peter Attia, 111:06)

Notable Quotes and Memorable Moments

| Timestamp | Speaker | Quote/Moment | |---------------|-------------|------------------| | 05:12 | Dr. Chang | "Harvey Cushing was just the starting point of modern neurosurgery..." | | 10:17 | Dr. Chang | "The force of evolution is guiding us towards things that are more minimally invasive..." | | 12:01 | Dr. Chang | "We're now moving from an era where we use a visualization of the histology now to this molecular profiling, which is more mechanistic." | | 23:03 | Dr. Chang | "The brain itself, which is processing that information in the body, actually doesn't have those [pain] receptors itself." | | 28:05 | Dr. Chang | "There is some really expensive real estate in there, and there's also some cheaper real estate." | | 30:11 | Dr. Chang | "What happens is some neurons get lost over time and then others will compensate in terms of that function." | | 40:26 | Dr. Chang | "Replacing function has never really been possible until very recently." | | 53:27 | Dr. Chang | "...a convergence of what’s possible with electrical engineering, high bandwidth wireless... sensors on a substrate thinner than a piece of paper" | | 72:58 | Dr. Chang | "[Ann] was one of our participants... We could essentially reconstruct her words from her neural activity—even after not speaking for 18 years." | | 92:23 | Dr. Chang | "Biology has solved a lot of these scaling problems. Cells that have the same genetic programming... end up having different identity, different purpose." | | 95:11 | Dr. Chang | "Let's get a couple of these [solutions] across the finish line so that they're actually out in the world helping people." | | 111:06 | Peter Attia | "There is really an opportunity to bend the arc of civilization by choosing a career in medicine. And what you’re doing, Eddie, is really on the forefront..." |

Important Timestamps for Deep Dives

• Neurosurgery foundations: 03:28 – 06:26
• Awake craniotomy/brain mapping: 18:59 – 24:21
• GBM genetics & immunotherapy: 11:19 – 16:34
• Corpus callosotomy/brain plasticity: 32:09 – 36:15
• Principles of BCIs: 39:13 – 54:01
• Case study with “Ann”—restoring speech: 61:01 – 86:48
• The future: new biologic and engineering frontiers: 91:04 – 104:54
• Inspiration for choosing medicine: 111:06 – 112:06

Takeaways

• Modern neurosurgery is a blend of tradition and radical innovation—combining old tools (craniotomy) with molecular biology, minimally invasive techniques, and now digital engineering.
• Brain-computer interfaces, once science fiction, are now functioning prototypes, radically altering possibilities for paralyzed and voiceless patients.
• The most transformative advances in coming years will likely come from the confluence of neuroscience, engineering, material science, and biology—requiring broad, interdisciplinary teams.
• The philosophical questions—about consciousness, identity, and the essence of human function—are as pressing as the technical challenges.
• There is immense opportunity for a new generation to shape the field and bring about therapies and technologies that even its founders could not have imagined.

Resources and Further Reading

• UCSF Neuroengineering research (Dr. Chang’s lab)
• 2023 Nature paper on BCI and speech restoration
• Peter Attia’s newsletter and Drive podcast archives

This summary seeks to encapsulate the central themes, technical insights, and inspirational vision Dr. Chang and Dr. Attia shared for listeners curious about the future of neurosurgery and neuroengineering.