Introduction: Unconventional Intelligence

• Biology demonstrates intelligence at all organizational levels, with agents solving problems in diverse spaces beyond the 3D world.
• Neuroscience is an elaboration of an ancient computational capacity arising from developmental bioelectricity.
• Bioelectricity enables cell collectives to navigate “morphospace” (the space of anatomical configurations).
• Multi-scale competency architecture means all levels can perform their own goal driven activties and is is exciting for novel engineering.

Examples of Problem Solving in Non-Traditional Spaces

• Planaria adapt to barium by altering gene expression, demonstrating problem-solving in “transcriptional space.” No evolutionary advantage exists as planeria would not have encounted barium in the wild, indicating how did cells “know” what genes to toggle?
• Tadpoles with eyes grafted onto their tails can still see, showing functional plasticity despite altered body structure. Tadpoles and Caterpillars have bodies changing and demonstrate memory persistance through drastic changes.
• Planaria can regenerate any body part and its tail demonstrates imprinted data after being headless. Planaria demonstrates memory spreading beyond brains.
• These examples challenge the notion of fixed developmental programs and highlight the adaptive capacity of biological systems.

Cells as Competent Problem Solvers

• Single-celled organisms (like Lacrymaria) exhibit remarkable control and problem-solving at the individual cell level.
• Multicellular organisms scale up this cellular competence to achieve complex morphogenesis (building body forms).
• teratoma a growth showing correct tissues (skin, muscle, hair, etc.) but lacking spatial organization demonstrating hardwares correct, but the anatomical positioning missing
• Morphogenesis isn’t just “forward emergence”; it’s intelligent, achieving goals via varied paths despite perturbations (William James’s definition of intelligence).
• Axolotls regenerate limbs, demonstrating the ability to achieve a specific anatomical target from different starting points.
• Kidney Tubules forming despite drastically varying numbers of cells making use of cell-cell commincation in normal circumistances and cyctoskelatal bending in mutated oversized cellls.
• picasso tadpoles moving organs to turn from “picasso tadpoles” with missplaced face parts into standard frogs indicating a goal, rather than hardcoded movements
• Evolution produces problem-solving machines, not just hardwired solutions, enabling adaptability.

Bioelectricity as the “Cognitive Glue”

• Bioelectricity is a key mechanism for coordinating cell activities into a collective intelligence.
• It’s not just for brains; all cells use bioelectrical signaling, a system predating nervous systems (evolved from bacterial biofilms).
• Cells have ion channels and electrical synapses (gap junctions), similar to neurons, but operating more slowly.
• Levin’s lab developed tools to observe and manipulate bioelectrical gradients in vivo, analogous to optogenetics in neuroscience.
• They control network topology (gap junctions) and electrical states (ion channels) using drugs, light, and other techniques.
• Monitoring involves voltagae and observing them by fluorescent voltage reporter dyes (simlar methods as zebra fish and mice)
• They also do bioelectrial intervention with specific RNA that prevent decoupling, or other that encourage it, as necessary.

Bioelectrical Control of Development and Regeneration

• Oncogenes cause cells to depolarize and disconnect, leading to tumors. This can be prevented by manipulating ion channels. The *electrical* state, not the oncogene itself, dictates the outcome.
• The “electric face” in frog embryos pre-patterns anatomical features *before* gene expression. Bioelectrical patterns guide cell behavior.
• By manipulating bioelectrical states, researchers can induce ectopic organs (eyes, limbs, hearts, brains) in tadpoles, demonstrating control over large-scale anatomy. They can also correct birth defects by restoring the correct bioelectrical “memory.”
• frog embryo experiment changing where “build an eye here” usually sits within an embryo, and cells comply creating eyes with lens, retina, and optical nerve.
• Planaria provide a model for studying bioelectrical pattern memory. The “target morphology” (number of heads) is stored in a stable, rewritable bioelectric circuit, *separate* from the anatomy and genome.
• This bioelectrical memory can be manipulated to create two-headed worms, or even revert head shapes to those of *other* planarian species (demonstrating access to latent morphogenetic possibilities).
• Limb regeneration in frogs can be induced by applying a cocktail of ion channel drugs, triggering a bioelectric state that initiates limb regrowth.
• Bioelectrical manipulations have stable, conditional, long term re-writeable recall and guide cells as it decides the body’s structure.

Synthetic Biology and the Origins of Collective Goals

• A fundamental question is where collective goals come from, and how cell collectives settle on specific targets.
• Testing by combining 2 groups with cells: cell A “make a flat head” and cell B “build a round head”, is impossible to infer without testing if A>B or B>A or something in between.
• To explore this, researchers created “Xenobots” – novel organisms from isolated frog skin cells (Xenopus laevis).
• Cells, not normally the goal or outcome from an isolated tadpole, spontenously forms proto organisms which could mean skin’s “default” behaviour is a xentobot (previous asks said bioelectricity is the main reason, clarify?)
• Liberated from their normal environment, these cells reboot their multicellularity and form motile, self-organizing structures.
  • Xenobots exhibit complex behaviors: movement, navigation, interactions, and even rudimentary maze-solving.
• Xenobots also show regenerative capacity, reforming after being cut in half. They exhibit calcium dynamics, even without neurons.
• Calcium flashes between xentobots are communication?
• The genome of xenobots is 100% *Xenopus laevis*, highlighting that these novel behaviors are not encoded directly in the DNA, but emerge from the cells’ inherent plasticity and self-organizing capacity.
• where this “goal” and outcomes “appears” in 48hrs is not entirely understood.
• testing is being conducted, and can show cognition tests, training, learning, and many other behaviors is not explained.

Implications for Bioengineering and Beyond

• Bioengineering allows manipulation at all levels of organization: cellular, organ/organism, and collective.
• Creating Cyborgs, Hybrid Agents with diverse configurations/cognitive capacity
• This opens up a vast “option space” of novel agents, blurring the lines between natural and artificial.
• Chimeric bioengineering can reveal how collective goals emerge and how minds and bodies map to each other.
• It pushes our thinking about Ethics when relating to beings made in unfamiliar ways (evolved? engineered? bioengineered? AI? how to decide?)
• Multiscale competency architecture, with bioelectrical networks, allows individual cells with local goals to scale up into collectives solving larger problems.

Conclusion

• Morphogenesis is an ancient proto-cognitive process, exhibiting problem-solving across multiple scales.
• Synthetic biology demonstrates we can’t easily predict the behavior of large collectives, even if we know about the individual subunits.
• This work challenges traditional notions of “organism,” “machine,” and “robot,” necessitating new ways of thinking about agency and ethics.
• “mind” and “body” distinctions are going to change, and evolve to become a “continuum”.

导言：非传统智能

• 生物学在所有组织层面上都展现出智能，各种主体在超越三维世界的不同空间中解决问题。
• 神经科学是对源于发育生物电的古老计算能力的一种详细阐述。
• 生物电使细胞群体能够在“形态空间”（解剖构型的空间）中导航。
• 多尺度能力架构意味着所有层级都可以执行它们自己的目标驱动活动，这对于新型工程设计来说是令人兴奋的。

非传统空间中解决问题的例子

• 涡虫通过改变基因表达来适应钡，证明了在“转录空间”中的问题解决能力。由于涡虫在野外不会遇到钡，因此不存在进化优势，这表明细胞是如何“知道”要切换哪些基因的？
• 将眼睛移植到尾巴上的蝌蚪仍然可以看见，显示出尽管身体结构改变，但功能可塑性依然存在。蝌蚪和毛毛虫的身体会发生变化，并表现出在剧烈变化中记忆的持久性。
• 涡虫可以再生任何身体部位，其尾巴在无头后仍表现出印记数据。涡虫证明了记忆可以超越大脑传播。
• 这些例子挑战了固定发育程序的概念，并突出了生物系统的适应能力。

细胞作为有能力的解题者

• 单细胞生物（如喇叭虫）在单个细胞水平上表现出卓越的控制和解决问题的能力。
• 多细胞生物将这种细胞能力放大，以实现复杂的形态发生（构建身体形态）。畸胎瘤是一种显示正确组织（皮肤、肌肉、毛发等）但缺乏空间组织的生长物，表明硬件正确，但解剖定位缺失。
• 形态发生不仅仅是“前向涌现”；它是智能的，通过各种路径实现目标，尽管存在扰动（威廉·詹姆斯对智能的定义）。
• 蝾螈再生四肢，展示了从不同起点实现特定解剖目标的能力。肾小管的形成尽管细胞数量差异很大，但在正常情况下利用细胞间通讯，在突变的超大细胞中利用细胞骨架弯曲。
• 毕加索蝌蚪移动器官，从面部器官错位的“毕加索蝌蚪”变成标准青蛙，这表明存在目标，而不是硬编码的运动。
• 进化产生的是解决问题的机器，而不仅仅是硬连接的解决方案，从而实现适应性。

生物电作为“认知粘合剂”

• 生物电是将细胞活动协调成集体智能的关键机制。
• 它不仅仅用于大脑；所有细胞都使用生物电信号传导，这是一个早于神经系统的系统（从细菌生物膜进化而来）。
• 细胞具有离子通道和电突触（间隙连接），类似于神经元，但运行速度较慢。
• 莱文的实验室开发了在体内观察和操纵生物电梯度的工具，类似于神经科学中的光遗传学。
• 他们使用药物、光和其他技术控制网络拓扑（间隙连接）和电状态（离子通道）。监测涉及电压，并通过荧光电压报告染料观察它们（类似于斑马鱼和老鼠的方法）。
• 他们还进行生物电干预，使用特定的RNA来防止解耦，或根据需要鼓励解耦。

生物电对发育和再生的控制

• 癌基因导致细胞去极化和断开连接，导致肿瘤。这可以通过操纵离子通道来预防。决定结果的是电状态，而不是癌基因本身。
• 青蛙胚胎中的“电面”在基因表达之前就预先模式化了解剖特征。生物电模式指导细胞行为。
• 通过操纵生物电状态，研究人员可以在蝌蚪中诱导异位器官（眼睛、四肢、心脏、大脑），展示了对大规模解剖结构的控制。他们还可以通过恢复正确的生物电“记忆”来纠正出生缺陷。青蛙胚胎实验改变了通常位于胚胎中的“在这里构建一只眼睛”的位置，细胞会遵从，创造出具有晶状体、视网膜和视神经的眼睛。
• 涡虫为研究生物电模式记忆提供了一个模型。“目标形态”（头部的数量）存储在一个稳定的、可重写的生物电回路中，与解剖结构和基因组分开。
• 这种生物电记忆可以被操纵来创造双头蠕虫，甚至可以将头部形状恢复为其他涡虫物种的形状（证明可以访问潜在的形态发生可能性）。
• 通过应用离子通道药物混合物，可以诱导青蛙的肢体再生，触发启动肢体再生的生物电状态。
• 生物电操纵具有稳定、有条件、可长期重写的记忆，并在细胞决定身体结构时引导细胞。

合成生物学与集体目标的起源

• 一个基本问题是集体目标来自何处，以及细胞群体如何确定特定目标。
• 通过将两组细胞组合起来进行测试：细胞 A“制造一个扁平的头”，细胞 B“构建一个圆形的头”，如果不进行测试，就无法推断 A>B 或 B>A 或介于两者之间的某个值。
• 为了探索这一点，研究人员创造了“异种机器人”—— 来自孤立青蛙皮肤细胞（非洲爪蟾）的新型生物体。这些通常不是从孤立蝌蚪中获得的目标或结果的细胞，会自发形成原生物体，这可能意味着皮肤的“默认”行为是异种机器人（以前的提问说生物电是主要原因，是否需要澄清？）
• 从正常环境中解放出来后，这些细胞会重启它们的多细胞性，并形成运动的、自组织的结构。异种机器人表现出复杂的行为：运动、导航、交互，甚至基本的迷宫求解。
• 异种机器人还表现出再生能力，在被切成两半后会重新形成。它们表现出钙动力学，即使没有神经元也是如此。异种机器人之间的钙闪烁是否是通讯？
• 异种机器人的基因组是 100% 的非洲爪蟾，这突出表明这些新行为并非直接编码在 DNA 中，而是源于细胞固有的可塑性和自组织能力。 这种“目标”和结果在 48 小时内“出现”在哪里，目前还没有完全理解。正在进行测试，并且可以显示认知测试、训练、学习和许多其他行为，但尚未解释。

对生物工程及其他领域的影响

• 生物工程允许在所有组织水平上进行操纵：细胞、器官/生物体和集体。
• 创建半机械人、具有各种配置/认知能力的混合主体。
• 这打开了一个广阔的新主体“选项空间”，模糊了自然与人工之间的界限。
• 嵌合生物工程可以揭示集体目标是如何出现的，以及思想和身体如何相互映射。这促使我们思考与以不熟悉的方式（进化？工程设计？生物工程设计？人工智能？如何决定？）制造的生命体相关的伦理。
• 具有生物电网络的多尺度能力架构，允许具有局部目标的单个细胞扩展成解决更大问题的集体。

结论

• 形态发生是一个古老的原始认知过程，在多个尺度上表现出解决问题的能力。
• 合成生物学表明，即使我们了解单个亚基，我们也无法轻易预测大型群体的行为。
• 这项工作挑战了“生物体”、“机器”和“机器人”的传统概念，需要用新的方式思考自主性和伦理。
• “思想”和“身体”的区别将会改变，并演变成一个“连续体”。