Session IV — Nobel Laureate Panel Discussion I
Breakthroughs Don’t Travel in Straight Lines
Three Nobel laureates — Carolyn Bertozzi (Chemistry 2022), Randy Schekman (Physiology/Medicine 2013), and Thomas Südhof (Physiology/Medicine 2013) — on what’s working, what’s hyped, and what they’d tell their younger selves. Moderated by Joseph Wu (Stanford).
Current Research Directions
- Bertozzi: The glycocalyx as a transport problem — a new blood-brain barrier shuttle from glycoscience
- Schekman: (1) Extracellular vesicles as biomarkers — trillions of “little sentinels” for early cancer detection; (2) Parkinson’s — running ASAP (Aligning Science Across Parkinson’s) with Sergey Brin’s family office, 150+ lab network
- Südhof: From how synapses release to how connections form — and what goes wrong in schizophrenia and Alzheimer’s. Frontier: drugs that promote synaptic connectivity
The Translation Cliff
- Bertozzi: The single most common failure mode: the biology doesn’t translate. PK divergence, species differences. Fixable if you survive the runway — in this funding climate, you usually can’t.
- Schekman: Animal models for neurodegeneration are a “persistent embarrassment.” Newer alpha-synuclein knock-in mice are finally recapitulating Parkinson’s progression.
- Bertozzi (solutions): Better organoids, humanized transgenics, lower regulatory barriers for Phase 0 human studies.
The Amyloid Cautionary Tale
- Amyloid plaques are removable by antibodies — but removal does not reliably reduce dementia
- Most Alzheimer’s patients carry APOE4/APOE3 defects, not APP mutations — decades and billions spent on the wrong frontier
- ASAP’s design principle: lots of shots on goal; don’t repeat the amyloid mistake with Lewy bodies in PD
- Brightest near-term target: LRRK2 — 30+ biotechs, including Denali’s brain-penetrant kinase inhibitor
- Südhof excited about Montara (Kevan Shokat’s brain-only delivery platform, including brain-only LRRK2 inhibitor)
Exosomes: Diagnostics Yes, Delivery No
- Schekman (diagnostics): Genuinely excited — a startup detecting stage-one ovarian cancer by reading three tumor antigens on individual particles
- Schekman (delivery): Skeptical to dismissive — exosomes lack a fusogen; they get internalized, dumped to the lysosome, and degraded
How to Start a Company from Academia
- Bertozzi: Start as SAB/consultant → find unmet need at your science intersection → spin out only with a technical co-founder from your own bench
- Südhof: Co-found if you must — but only take the CEO seat if you’d genuinely enjoy it
- Schekman: His yeast secretion work (1970s) led to 30% of the world’s recombinant insulin — he never ran the experiment himself
Funding the Gap
- Philanthropy (ASAP) can do targeted miracles but can’t replace the NIH
- Hybrid academic-industry models (GSK-Harvard, Stanford-Takeda) die on leadership turnover
- Until incentive alignment improves, “keep submitting grants”
Advice to Young Scientists
- Follow the question, not the application
- Don’t romanticize the executive role
- Find a technical co-founder from your own bench
- Take the human-translation problem personally
- Resist the dominant hypothesis
- Aim at what no one knows how to do yet
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