## ---- > Ethical Frontiers of Post-Mortem Brain Research,Brains sustained for **~24 hours**. **📅 Date:** ➤ ⌈ [[2025-07-19-Sat〚🧠 Bexorg Rebooting the Human Brain(~24) & (Pig Brain Research) ▪ Frankenstein Quotes〛]]⌋ **👤 Who**： [[The HW Project Research List]] **💭 What:** ➤ #👾/Thoughts ? - The brain doesn’t die — it falls silent. And we’re learning how to listen again. - There was no spark of consciousness… but the tissue was alive. - We are at the edge of something medicine has never dared to touch. ➤ One of my deepest fears in middle school after reading the book 《织梦人》 If I were a brain in the jar... and here you go ... not helping #👾/Comment **👀 Snap:** >[!note] #👾/Comment ![[Pasted image 20250720223543.png|#left|200]] I’ve always been fascinated by the true meaning of death — especially _brain death_. What does it mean when someone is declared physically dead, yet residual signals still flicker from their brain? If neurostimulation could one day revive such a brain, or restore activity without memory — creating a person entirely different from before — would we still consider that the same “self”? Or imagine a future where a human brain is preserved and transplanted into a robotic body, modeled after someone we loved. Would that still be “you”? This echoes the ancient paradox of the Ship of Theseus — if you replace every plank of a ship, at what point is it no longer the same ship? Or perhaps, at a higher level, the question itself dissolves — identity isn’t fixed in the parts, but flows through experience, memory, and meaning. Sometimes I feel that the “sources” I’ve encountered in life — books, films, fragments of conversation — later reveal themselves as foreshadowing, as if leaving breadcrumbs. _Source Code_ comes to mind. And it feels fitting that my first English literature book was **Frankenstein**[^1] — a metaphor I now see mirrored in my obsession with consciousness, identity, and the untold frontiers of the brain. ![[Pasted image 20250720223439.png|#left|300]] ➤ Reminds me of the movie 《Source Code》 ![[Pasted image 20250720221907.png|#left|200]] ⇩ 🅻🅸🅽🅺🆂 ⇩ **🏷️ Tags**: #HW/Pool #🧠/Neuro-Science #🔭Sci-Fi/Reality **🗂 Menu**: ⌈[[✢ M O C ➣ 07 ⌈J U L - 2 0 2 5⌉ ✢|2025 - J U L- MOC]]⌋ ⌈[[✢ L O G ➢ 07 ⌈J U L - 2 0 2 5⌉ ✢|2025 - J U L - LOG]]⌋ #👾/Private ------➤ ⌈[[🧬 Rigor Mortis-What Happens to Muscles After Death (👨‍🦲 & 🐵)]]⌋ ------➤ ⌈[[🧬 ATP Production – Cellular Energy Generation]]⌋ ------➤ ⌈[[Nysten's Rule (（尼斯腾法则-尸僵顺序规律) -Rigor Mortis Progression]]⌋ ------➤ ⌈[[FDA Medical Device Approval Process (13 Steps)]]⌋ **🌐 Link**: [Endpoints News](https://endpoints.news/rebooting-dead-human-brains-biotech-seeks-to-reinvent-drug-testing-work/) **🔗 Related Research** - **2019 Nature paper** on pig brain restoration: [Nature: Restoration of pig brain circulation](https://www.nature.com/articles/s41586-019-1099-1) - **FDA’s shift away from animal models** (2025): [FDA plan for organoids & simulations](https://endpoints.news/fda-unveils-plan-to-replace-animal-testing-with-organoids/) --- ## 📍 I. Overview: ### 1. What is Bexorg? - A biotech startup based in **New Haven, Connecticut**, spun out of **Yale University**. - Founded by **Zvonimir Vrselja** and **Nenad Sestan**. - Uses a system called **BrainEx** to **perfuse and sustain human brains** shortly after death for drug testing. - Aims to **address the translational gap** in neuroscience drug development. ![[Screenshot 2025-07-20 at 22.23.19.png|400]] --- ### 2. 🧪 Project Overview - **Objective:** - To sustain human brains post-mortem for drug testing, without restoring consciousness. - **Founder:** - Zvonimir Vrselja (co-founder & CEO), based on research from Nenad Sestan’s lab at Yale. - **Startup:** - Bexorg, launched to bring brain perfusion technology to scale. - **Use Case:** - A new model for neuroscience drug testing, addressing failure rates in animal trials. ### 3. Key Methodology - Brains are **removed post-mortem （尸检）**, sedated, and fed with **oxygenated artificial blood**. - Brains are kept “biologically active” for **~24 hours** but have **no consciousness or electrical firing**. - Sensors monitor molecular activity, drug response, and biomarker release in real-time. --- ### 4. 🧬 Key Advantages 1. **Precision Dosing**: - Ability to assess the right dose by direct perfusion. 2. **Drug Efficacy & Safety**: - Measures impact of drugs on neurons and protein expression. 3. **Predictive Value**: - Tests correlate well with known clinical trial data. 4. **Ethical Alternative**: - Aims to reduce reliance on animal testing, especially primates. --- ## II. 🧠 Neuroscience Insights ### 1. Brain & Death - Brain decay is **not binary**; cells can be revived post-mortem. - Challenges the traditional definition of **brain death**. - Allows study of **connectomics** (brain wiring) in donated human tissue. ### 2. 🧬 Core Technology: BrainEx System - **Perfusion Platform:** - Artificial blood perfuses human brains removed post-mortem. - **Sustained Functionality:** - Maintains **cellular and molecular activity** (e.g. DNA transcription, metabolism). - **No Consciousness:** - All brains are sedated; no organized electrical activity is present. - **Duration:** - Brains sustained for **~24 hours**. - **Monitoring:** - Real-time sensors track pressure, blood flow, molecule release. - Laser-based systems assess drug absorption. - “Secretome” analysis helps identify biomarkers and track drug efficacy. - **Organs Used:** Donated brains from organ procurement orgs, with full consent. ### 3. 🧠 Pig Brain Research & Why It Works - **Initial Proof-of-Concept:** - 2019 Nature paper demonstrated restored cellular activity in pig brains hours post-decapitation. - **Key Insight:** Brain death is **not binary** — decay is gradual and reversible under certain conditions. - **Success Factors:** - Artificial perfusion mimics heart, lungs, kidneys, and immune system. - Neurons preserved despite cessation of global brain activity. - **Application:** - Now scaled to human brains to simulate brain response in clinical settings. --- ### 🚫 Consciousness & Ethics - Brains are **intentionally sedated** to prevent any chance of awareness. - The bioethics board** includes experts from Stanford and Harvard to manage public trust and safety concerns. - All brains are **consented donations** via organ procurement organizations. ![[Screenshot 2025-07-20 at 22.39.31.png]] --- ### 💡 Use Case: Biohaven Partnership - Tested Alzheimer’s and ALS drugs on disease-specific brains. - Identified unexpected **dose responses and biomarker patterns**. - Helped pivot clinical strategy and save time/cost in human trials. --- ### 📈 Future Vision (during the time of the article published) - Running ~**1000 brains/year** planned for 2026. - Building **AI models** for neuroscience drug discovery. - Exploring gene therapy delivery into the brain via AAV vectors. --- ### 🧭 Reflections > “This is one of the closest things to investing in science fiction.” – David Beyer, Amplify Partners > “These are not living brains. They are not conscious. But they can tell us things no animal model can.” – Z. Vrselja --- ![[Screenshot 2025-07-20 at 22.38.27.png]] --- [^1]: [[📘 Frankenstein — Selected Quotes]]