The Dissenter

#1235 Nicole Rust: Why Neuroscience Hasn’t Solved Brain Disorders―and How We Can Change That

Apr 2, 2026
Guest
Nicole C. Rust
Nicole Rust, a Penn psychology professor who studies memory, mood and neural computation. She explores why molecular neuroscience often fails to produce cures, contrasts reductionist and complex systems frameworks, traces the serendipitous history of psychiatric drugs, and argues for dynamical, multi‑level models and AI tools to rethink how we find and test brain treatments.
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INSIGHT

Computer Metaphor Explains Perception But Not Many Disorders

  • The serial computer metaphor helps explain sensory computations but poorly maps to disorders like insomnia or anorexia.
  • Rust argues dysfunction often reflects imbalances or calibration failures, not simply computational errors.
ANECDOTE

How Dog Narcolepsy Led To A New Insomnia Drug

  • The orexin discovery began with dog narcolepsy genetics and led to Merck screening ~2 million compounds to create suvorexant for insomnia.
  • Rust uses this bench-to-bedside arc to show how decades of basic work plus huge industry effort produced a new sleep drug.
ANECDOTE

Antipsychotics Originated From An Antihistamine Accident

  • Chlorpromazine was discovered when an antihistamine produced calming sedation and was repurposed to treat psychosis in the 1950s.
  • Rust highlights that most antipsychotics since are refinements on that original serendipitous mechanism.
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