Introduction: Body’s Intelligence and Bioelectricity

• Our bodies demonstrate “everyday magic”: High-level mental goals translate into physical actions (like muscle depolarization) via the body’s electrical system.
• Concept: “Words and drugs have the same mechanism of action” (Benedetti) – mind and body are interconnected, crucial for future medicine.
• We are “collective intelligences”: Composed of many components (cells, molecular networks) that possess their own “agendas” and a form of intelligence.
• Even single cells and molecular networks within them show learning (e.g., Pavlovian conditioning), demonstrating intelligence is basic.
• Body functions as “multi-scale competency architecture”: Various levels (molecular networks, cells, tissues, etc.) solve problems in different “spaces,” not just a nested structure.

The Anatomical Compiler: A Future Vision

• Long-term medical goal: “Anatomical compiler” – A system to design and build any anatomical structure by specifying its desired form (drawing it).
• This would solve birth defects, injuries, cancer, aging, etc., by conveying our goals to groups of cells. We will learn how to tell cells, specifically, what to build.
• This isn’t a “3D printer” (micromanaging cells), but a “communications device,” a translator between our goals and the cells’ collective goals.
• DNA doesn’t fully code for patterns, just protein “hardware.” The “physiological software” directs growth; genetic information isn’t enough (frog/axolotl hybrid example).
• Biology is like 1940s computer science: Focus is on hardware. We must focus on the body’s “reprogrammability” and “problem-solving capacity,” analogous to modern software.

Intelligence and Problem Solving in Biology

• Intelligence: “Ability to reach the same goal by different means” (William James). It is about having competencies to reach some kind of goals and this may often requires plasticity, to adapt to new situation and events. Not human-level intelligence, but objective, problem-solving competence.
• Biological intelligence exists in many “spaces”: 3D space (animal movement), transcriptional space (gene expression), physiological state space, anatomical “morphospace”.
• Cells show remarkable problem-solving: Planaria adapting to barium exposure; tadpole faces rearranging to a normal frog face even after radical disruption (“Picasso tadpoles”).

Bioelectricity: The Interface to Morphogenesis

• The nervous system inspires understanding of cell communication: Ion channels, voltage gradients, electrical synapses.
• All cells are electrically active, not just nerve cells, with gap junctions forming networks. The cellular collective thinks about how to maintain and control anatomy using bioelectriicty.
• These networks “navigate anatomical space” to build and maintain the body. The project aims to learn “to interpret these [electrical signals].
• Developmental tools developed by levin to read bioelectric signals include voltage-sensitive fluorescent dyes and using compuer simultions to map voltages, gene expression and to observe and anayze patterns.
• “Electric face” pattern in frog embryos: Bioelectric pre-pattern dictates future organ placement.
• Abnormal voltage pattern seen in cancer cells even *before* a tumor develops.
• Levin developed toold and methodes to “read” (the above voltage signals) as well as “write”: controlling gap junctions and ion channels.
• Controlling voltage patterns (using ion channels, optogenetics, pharmacology) can induce organ formation (eyes, limbs, etc.).
• Key features: It’s *instructive* (controls outcomes), *modular* (don’t need to micromanage steps, just “call a subroutine”), and demonstrates collective behavior (cells recruiting other cells).

Regeneration, Birth Defects, and Cancer Applications

• Frog leg regeneration triggered by a bioelectric cocktail, resulting in substantial leg regrowth (“injury mirroring” phenomenon observed). This works at a distance from the site of injury.
• Discolsure: This company *Morphoceuticals*: using of this kind of stimulation on patients (hopeful).
• Birth defects (in frog brain, caused by teratogens or genetic mutations) can be *repaired* by adjusting the bioelectric pattern, even with genetic problems, acting in effect through *software*, which the patterns constitute.
• Tool Called Eden “The Electoceutical Design Enviroment”. Use of bioelectirc interfaces to design and execute treatment (including pharmaceutical).
• Cancer cells: “Dissociative identity disorder” – disconnected from the electrical network, returning to small, single-cell goals.
• Possible detection of cancerous cells by observing bioelectric activity that is precancerous/early-cancer.
• Potential for cancer treatment via forced reconnection of cancer cells to the network (normalization, not destruction). This happens independent of genetic intervention or change, which is very useful, it works even if you don’t “fix the genes.”
• Anthrobots (human biobots): Human tracheal cells spontaneously form motile structures with unique properties, including neural wound healing.

Conclusion: Towards Top-Down Interventions

• Biomedicine is undergoing transformation by adopting and recognizing that collective behaviors must be understood to manipulate multicellular systems.
• Rate-limiting step in transformative medicine: Communicating goals to cellular “swarms”, viewing them as agents with agendas.
• Genetics/Big Data are insufficient; crisper still has “which gene do we crisper/change”? This is all part of the larger picture of taking the *top down* approach of using collective intelligence to manage.
• Roadmap comes from behavior science and neuroscience: Exploiting the “software of life” via top-down control, resetting cell goals (not micromanaging them molecularly).
• Bioelectric interface: Key to cell intelligence (like in the nervous system), with emerging tools for its application in diverse areas.
• AI will make *top down* medicine viable by utilizing top down tools, goals propagated and cascaded throughout intelligent tissues to solve for, like cancer, injuries and other goals.

导言：身体的智慧与生物电

• 我们的身体展现出“日常魔法”：高级心理目标通过身体的电系统转化为身体动作（如肌肉去极化）。
• 概念：“言语和药物具有相同的作用机制”（Benedetti）——身心相连，对未来医学至关重要。
• 我们是“集体智慧”：由许多具有自身“议程”和某种形式智能的组成部分（细胞、分子网络）组成。
• 即使是单个细胞和其中的分子网络也显示出学习能力（例如，巴甫洛夫条件反射），表明智能是基本的。
• 身体充当“多尺度能力架构”：各个层面（分子网络、细胞、组织等）在不同的“空间”中解决问题，而不仅仅是嵌套结构。

解剖编译器：未来的愿景

• 长期医学目标：“解剖编译器”——一个通过指定其所需形式（绘制它）来设计和构建任何解剖结构的系统。
• 这将通过向细胞群传达我们的目标来解决出生缺陷、损伤、癌症、衰老等问题。 我们将学习如何具体地告诉细胞要构建什么。
• 这不是一个“3D打印机”（微观管理细胞），而是一个“通信设备”，一个我们的目标和细胞集体目标之间的翻译器。
• DNA并不完全编码模式，只编码蛋白质“硬件”。 “生理软件”指导生长；遗传信息是不够的（青蛙/蝾螈杂交例子）。
• 生物学就像20世纪40年代的计算机科学：重点是硬件。 我们必须关注身体的“可重编程性”和“解决问题的能力”，类似于现代软件。

生物学中的智能和问题解决

• 智能：“通过不同方式达到相同目标的能力”（William James）。它是关于拥有达到某种目标的能力，这通常需要可塑性，以适应新的情况和事件。不是人类层面的智能，而是客观的、解决问题的能力。
• 生物智能存在于许多“空间”中：3D空间（动物运动）、转录空间（基因表达）、生理状态空间、解剖“形态空间”。
• 细胞表现出非凡的问题解决能力：涡虫适应钡暴露；即使在彻底破坏后，蝌蚪的脸也会重新排列成正常的青蛙脸（“毕加索蝌蚪”）。

生物电：形态发生的接口

• 神经系统激发了对细胞通讯的理解：离子通道、电压梯度、电突触。
• 所有细胞都是电活跃的，不仅仅是神经细胞，间隙连接形成网络。细胞群体使用生物电来思考如何维持和控制解剖结构。
• 这些网络“导航解剖空间”来构建和维护身体。 该项目旨在学习“解释这些[电信号]”。
• 莱文开发的用于读取生物电信号的发育工具包括电压敏感荧光染料和使用计算机模拟来映射电压、基因表达并观察和分析模式。
• 青蛙胚胎中的“电脸”模式：生物电预模式决定了未来的器官位置。
• 甚至在肿瘤发展*之前*，癌细胞中就可以看到异常的电压模式。
• 莱文开发了“读取”（上述电压信号）以及“写入”的工具和方法：控制间隙连接和离子通道。
• 控制电压模式（使用离子通道、光遗传学、药理学）可以诱导器官形成（眼睛、四肢等）。
• 主要特点：它是*指导性的*（控制结果），*模块化的*（不需要微观管理步骤，只需“调用子程序”），并展示了集体行为（细胞招募其他细胞）。

再生、出生缺陷和癌症应用

• 青蛙腿再生是由生物电混合物触发的，导致大量的腿再生（观察到“损伤镜像”现象）。 这在远离受伤部位的地方起作用。
• 披露：这家公司 *Morphoceuticals*：在患者身上使用这种刺激（有希望）。
• 出生缺陷（在青蛙大脑中，由致畸剂或基因突变引起）可以通过调整生物电模式来*修复*，即使存在遗传问题，实际上也是通过*软件*起作用，这些模式构成了软件。
• 名为 Eden “电疗设计环境”的工具。 使用生物电接口来设计和执行治疗（包括药物）。
• 癌细胞：“分离性身份障碍”——与电网络断开连接，返回到小的、单细胞目标。
• 通过观察癌前/早期癌症的生物电活动来检测癌细胞的可能性。
• 通过强制癌细胞重新连接到网络（正常化，而不是破坏）来治疗癌症的潜力。 这种情况的发生独立于基因干预或改变，这非常有用，即使你不“修复基因”，它也有效。
• 人造机器人（人类生物机器人）：人类气管细胞自发形成具有独特属性的运动结构，包括神经伤口愈合。

结论：迈向自上而下的干预

• 生物医学正在经历变革，它采用并认识到必须理解集体行为才能操纵多细胞系统。
• 转化医学中的限速步骤：将目标传达给细胞“群”，将它们视为具有议程的主体。
• 遗传学/大数据是不够的；CRISPR 仍然有“我们 CRISPR/改变哪个基因”？ 这都是利用集体智能进行管理的*自上而下*方法的更大图景的一部分。
• 路线图来自行为科学和神经科学：通过自上而下的控制利用“生命软件”，重置细胞目标（而不是在分子上微观管理它们）。
• 生物电接口：细胞智能的关键（就像在神经系统中一样），具有新兴工具，可将其应用于各种领域。
• 人工智能将通过利用自上而下的工具、在智能组织中传播和级联的目标来实现*自上而下*的医学，以解决癌症、损伤和其他目标。