Two New Papers: Anthrobots and Embryo Communication

• Two papers published: One on “Anthrobots” (human-cell-based biobots) and one on “Cross-Embryo Morphogenetic Assistance” (CEMA) where embryos help each other develop.
• Common theme: Understanding biological information sources and collective decision-making in biology, beyond just the genome.

Anthrobots (Gizem’s Paper)

• Anthrobots are self-motile constructs made of *adult* human tracheal cells (not genetically modified – “wild type”).
• Represent a shift: Viewing nature as a *design medium* (synthetic biology). Biology offers self-construction, healing, carbon negativity.
• Challenge to traditional synthetic morphogenesis: Usually focuses on genetic editing, but anthrobots show epigenetic factors are also key. No genetic modification is used.
• Process: Human airway epithelial progenitor cells form spheroids. Cilia (hair-like structures) normally face inward. The key was flipping them *outward* for motility. Achieved by removing matrix and using retinoic acid.
• Key properties: Fully cellular (no wiring or mechanics), self-constructing from single cells, programmable anatomies (“biobots”).
• They can perform useful work, namely, inducing repair in damaged human neuronal tissue *in vitro*.
• Anthrobots demonstrate the plasticity of adult human cells, not just embryonic cells (like Xenobots, made of frog cells).
• Distinct “morphotypes” (shapes) and behaviors emerge, despite identical DNA, showing epigenetic influence. A relationship exists between shape/structure and resulting movements/motility.
• Medical potential: Personalized medicine; using patient’s own cells, potentially avoiding immune rejection. Could target inaccessible tissues, deliver drugs, clear plaques, etc. *Future* research needed for in vivo testing.
• Lifespan of weeks to months in cell-culture medium, ending with biodegradation.

Cross-Embryo Morphogenetic Assistance (CEMA) (Angela’s Paper)

• Embryos (Xenopus laevis, frog) in groups are *more resistant* to teratogens (development-disrupting substances) than single embryos.
• Addresses a knowledge gap: Lateral interactions between *whole organisms* influence development, not just cell/tissue/DNA level interactions.
• Significance: If the communication mechanisms, also named as “instructive cues” by the researches can be understood/harnessed to give instruction to cells on repair or growth, leading to huge potential future application in medicien
• Contradicts “genome-centric” view: Genome alone doesn’t determine everything; the *social environment* of embryos matters.
• Crazy because everything held constant except number of embryos but result show large difference/discrepency.
• “Wisdom of the crowds” effect *but*: Mixing teratogen-exposed and unexposed embryos doesn’t help. *All* embryos must experience the challenge for the protective effect.
• Robustness increases with group size: Survival *increases*, defect frequency *decreases*. Single embryos almost never survive.
• Important implications for toxicology studies: Many studies may *underreport* teratogen effects due to group correction.
• Current research: The ‘wave of information” between emryos is hypothesized to be by: an injury on a single cell within the collection of embryos which induces a calcium response to itself; calcium then induces an ATP to release into the media. nearby cells absorb this and themselves emit a calcium response.
• Mechanism: Communication is likely via calcium and ATP signaling. Blocking these *reduces* survival, mimicking singleton embryos.
• Inter-embryonic communication (signaling molecules) vs. inter-embryonic interaction (embryos growing together, allowing communication).
• Not limited to genetic homogeneity: Different frog lineages (wild-type and albino) show similar effects.
• Wildtype refers to natural or typical genetic information as they exist in the natural world with no modiciations from labs or scientists.
• Transcriptional changes (changes in RNA levels) are observed, indicating different coping mechanisms in large vs. small groups.

Broader Implications and Future Directions

• Biobot applications go beyond medicine (as described above) may also find applicatin for construction/architecture; biology can be scaled up.
• Medical potential to be faked, emulating signal inducing development and applying it “at-will” and by force, in patience that may have needs which relate.
• Basic research: Studying “basal cognition” and “diverse intelligence” in anthrobots (memory, learning, preferences).
• Understanding the “cognitive glue” that scales up individual intelligences (cells) to larger collective intelligences.
• Bioelectricty may hold importance.

两篇新论文：Anthrobots 与胚胎间通讯

• 发表了两篇论文：一篇关于“Anthrobots”（基于人类细胞的生物机器人），另一篇关于“跨胚胎形态发生协助”（CEMA），即胚胎互相帮助发育。
• 共同主题：理解生物学中的生物信息来源和集体决策，而不仅仅是基因组。

Anthrobots (Gizem 的论文)

• Anthrobots 是由 *成人* 人类气管细胞（未经过基因改造 – “野生型”）制成的自驱动结构。
• 代表了一种转变：将自然视为一种 *设计媒介*（合成生物学）。 生物学提供了自我构建、自愈、负碳排放等特性。
• 对传统合成形态发生的挑战： 通常侧重于基因编辑，但 Anthrobots 表明表观遗传因素也很关键。 未使用任何基因改造。
• 过程：人类气道上皮祖细胞形成球体。 纤毛（毛发状结构）通常向内。 关键是将它们翻转 *向外* 以实现运动。 这是通过去除基质并使用维甲酸来实现的。
• 关键特性：完全由细胞构成（无布线或机械结构），从单个细胞自构建，可编程的解剖结构（“生物机器人”）。
• 它们可以执行有用的工作，即 *在体外* 诱导受损人类神经元组织的修复。
• Anthrobots 证明了成人人类细胞的可塑性，而不仅仅是胚胎细胞（如 Xenobots，由青蛙细胞制成）。
• 尽管 DNA 相同，但出现了不同的“形态型”（形状）和行为，表明表观遗传的影响。形状/结构与由此产生的运动/活动性之间存在关系。
• 医疗潜力：个性化医疗；使用患者自身的细胞，可能避免免疫排斥。 可以靶向难以触及的组织，递送药物，清除斑块等。 *未来* 需要进行体内测试研究。
• 在细胞培养基中的寿命为数周至数月，最终以生物降解结束。

跨胚胎形态发生协助 (CEMA) (Angela 的论文)

• 群体中的胚胎（非洲爪蟾，青蛙）比单个胚胎 *更能抵抗* 致畸物（发育破坏物质）。
• 解决了一个知识差距：*整个生物体* 之间的横向相互作用影响发育，而不仅仅是细胞/组织/DNA 水平的相互作用。
• 重要性： 如果能够理解/利用这种通讯机制（研究人员也称之为“指示性线索”），向细胞发出修复或生长的指令，这将为未来的医学应用带来巨大潜力。
• 与“以基因组为中心”的观点相矛盾：仅靠基因组并不能决定一切；胚胎的 *社会环境* 也很重要。
• 很令人惊讶，因为除了胚胎数量外，其它一切都保持恒定，但结果却显示出很大差异。
• “群体智慧”效应 *但是*：混合暴露于致畸物和未暴露的胚胎没有帮助。 *所有* 胚胎都必须经历挑战才能产生保护作用。
• 稳健性随群体规模的增加而增加：存活率 *增加*，缺陷频率 *降低*。 单个胚胎几乎无法存活。
• 对毒理学研究的重要意义：许多研究可能由于群体矫正而 *低估* 了致畸物的影响。
• 目前的研究： 胚胎之间的“信息波”被假设为：群体内单个细胞受损会诱导自身钙反应；然后钙诱导ATP释放到介质中。 附近的细胞吸收这些并自身发出钙反应。
• 机制：通讯可能通过钙和 ATP 信号传导。 阻断这些信号 *会降低* 存活率，类似于单个胚胎。
• 胚胎间通讯（信号分子）与胚胎间相互作用（胚胎一起生长，允许通讯）是有区别的。
• 不限于遗传同质性：不同的青蛙谱系（野生型和白化型）表现出相似的效果。
• 野生型是指自然界中存在的自然或典型遗传信息，没有经过实验室或科学家的修改。
• 观察到转录变化（RNA 水平的变化），表明大群体与小群体中存在不同的应对机制。

更广泛的影响和未来方向

• 生物机器人的应用不仅限于医学（如上所述），也可能发现它适用于建筑/工程建造；生物学可以被扩大规模。
• 可能用以模拟诱导发育的信号并在有相关需要的患者中强行使用，未来可能具有虚假医疗用途。
• 基础研究：研究 Anthrobots 中的“基础认知”和“多样化智能”（记忆、学习、偏好）。
• 理解将个体智能（细胞）扩展到更大的集体智能的“认知粘合剂”。
• 生物电可能具有重要作用。