Introduction: Planarians and Regeneration

• Planarian flatworms are a model for regenerative medicine: They can regenerate any body part, including the brain, are highly cancer-resistant, and are biologically immortal (do not age). Understanding their regenerative mechanisms holds promise for human medicine.

Cancer as a Disruption of Cellular Communication

• Cancer is fundamentally a breakdown of multicellular cooperation, not simply a result of DNA mutations. Individual cells disconnect from the larger bioelectrical, chemical, and mechanical network that coordinates tissue organization.
• Disconnected cancer cells revert to a primitive, unicellular state, focusing on self-preservation and proliferation (like amebas), treating the rest of the body as an external environment.
• The “cognitive light cone” concept describes the scale of goals a cell or group of cells can pursue. In cancer, this light cone shrinks from the whole-body level to the individual cell level.
• The DNA provides instructions for making cellular “hardware”(proteins), *not* a direct blueprint for the body’s form and function. It creates components allowing complex and adaptable computation. The overall anatomical form comes about as the network (as the “software”)
• The analogy to computer hardware/software highlights that focusing solely on DNA (hardware) is insufficient for addressing many regenerative medicine challenges, analogous to fixing computer issues through soldering components alone.
• Focus should instead be on “reprogramming” the bioelectric signaling that directs cellular behavior (the “software”), by taking advantage of cellular natural existing behavior of cell’s computation.

Bioelectric Signaling and Pattern Memory

• Cells communicate through electrical signals using ion channels (protein gates) that control the flow of charged ions (sodium, potassium, chloride, protons). This is literal electricity.
• Groups of cells form bioelectrical networks similar to neural networks, storing memories and making decisions. These networks are essential for maintaining anatomical structure.
• The “target pattern” (correct body shape) is stored as a memory within this bioelectrical network. Cells actively work to minimize deviation from this pattern during regeneration.
• Fluorescent voltage-sensitive dyes can be used to visualize these bioelectrical patterns in living tissues, allowing researchers to observe defects associated with cancer, injury, or birth defects.
• The first step to cancer (with use of exmaples) includes cells disconnecting their bioelectrical signalling with their neighbor cells, leading to the ‘rolling back’ and cancer and it’s cancerous and invasive behaviors, even in spite of genetic makeup.
• Artificial re-connecting bioelectrical patterns show normalizing potential to cancerous properties, showing there exists ‘communcations’ to cells which guide them how to ‘behave’.
• The research goal is to develop computational models and “electroceutical” drugs (ion channel modulators) to correct aberrant bioelectrical patterns and restore normal tissue organization.

Implications and Examples

• The approach is *not* about killing cancer cells (like chemotherapy) but about restoring their cooperative behavior within the tissue. It also does not aim to “fix” DNA mutations.
• Frog experiments show that induced tumors (even with human oncogenes) can be suppressed or normalized by manipulating bioelectrical connectivity.
• GBM or Glioblastoma Multiforme (a brain cancer), is another application example, where “turning off” this bioelectrical signalling can revert cancer’s typical ‘rolling back’ cancer cellular activity, restoring them as an ‘ideal’ state as per thier normal function in context of the body’s multicellular function.
• Similar normalization of cancer cells has been observed in salamanders and mouse embryos, highlighting that this is a biological possibility, not just a theoretical concept.
• Planarians, with their messy genomes, demonstrate that perfect DNA is *not* required for robust regeneration and cancer resistance. Their cells have evolved to handle genomic noise.
• Cellular decisions are *not* solely driven by genetics and *are* made. They adjust and modify their behaviors in response to environmental stressors, including chemotherapy; they exhibit a basic form of intelligence (“basal cognition”).
• Problems exist in physiological nature (how cells remember what pattern to exist as) vs. purely DNA hardware. For example: mirroring pattern (e.g. mirror effect in epileptic brain) or even cardiac patterns of mis-regulation and re-triggering.

Addressing Common Misconceptions

• Family genetic predispositions (hardware): “protecting the hardware”. And inherited predispositions, play roles with likelihood.
• While maintaining healthy DNA (avoiding damage) is beneficial, it’s not the complete picture. Bioelectrical disruptions alone can cause cancer.
• Age and Cancer: increased loss of regenerative and electrical communication abilities lead to increase chances for cancer to rise.
• “Ion channel drugs” (electroceuticals), often already used for conditions like epilepsy, can be repurposed to modulate bioelectrical signals, potentially on a systemic level. This differs significantly from targeted therapies or electrical shocks.
• For adults, medication benefits (like blood pressure medications that affect ion channels) generally outweigh any theoretical risks related to bioelectrical disruption.
• For embryos, however, are subject to issues by taking some bioelectrical medication.
• Liver can regenerate (and do what planarians do). human can regenerate fingertips (the very tip-ends, the very distal parts of the finger body parts, and at an earlier-human stages of growth (kids vs. adult).

引言：涡虫与再生

• 涡虫扁形虫是再生医学的一个模型：它们可以再生任何身体部位，包括大脑，具有高度抗癌性，并且是生物学上不朽的（不会衰老）。了解它们的再生机制为人类医学带来了希望。

癌症作为细胞通讯的中断

• 癌症根本上是多细胞合作的崩溃，而不仅仅是DNA突变的结果。单个细胞脱离了协调组织组织的更大的生物电、化学和机械网络。
• 断开连接的癌细胞恢复到原始的单细胞状态，专注于自我保护和增殖（像变形虫），将身体的其余部分视为外部环境。
• “认知光锥”概念描述了细胞或细胞群可以追求的目标的规模。在癌症中，这个光锥从全身水平缩小到单个细胞水平。
• DNA提供了制造细胞“硬件”（蛋白质）的指令，而不是身体形态和功能的直接蓝图。它创造了允许复杂和适应性计算的组件。整体解剖形态是网络（作为“软件”）产生的。
• 与计算机硬件/软件的类比强调，仅仅关注DNA（硬件）不足以解决许多再生医学挑战，类似于仅通过焊接组件来解决计算机问题。
• 相反，重点应该是通过利用细胞计算的自然现有行为来“重新编程”指导细胞行为（“软件”）的生物电信号传导。

生物电信号传导和模式记忆

• 细胞通过使用离子通道（蛋白质门）控制带电离子（钠、钾、氯化物、质子）流动的电信号进行通信。这是真正的电。
• 细胞群形成类似于神经网络的生物电网络，存储记忆并做出决策。这些网络对于维持解剖结构至关重要。
• “目标模式”（正确的身体形状）作为记忆存储在该生物电网络中。在再生过程中，细胞积极地努力最小化与该模式的偏差。
• 荧光电压敏感染料可用于可视化活组织中的这些生物电模式，使研究人员能够观察与癌症、损伤或出生缺陷相关的缺陷。
• 癌症的第一步（以实例说明）包括细胞断开与相邻细胞的生物电信号，导致“回滚”以及癌细胞的癌性和侵袭性行为，即使在基因组成正常的情况下也是如此。
• 人工重新连接生物电模式显示出对癌细胞特性的正常化潜力，表明存在指导细胞如何“行为”的“通讯”。
• 研究目标是开发计算模型和“电药物”（离子通道调节剂）来纠正异常的生物电模式并恢复正常的组织组织。

意义和例子

• 这种方法不是杀死癌细胞（如化疗），而是恢复它们在组织内的合作行为。它也不旨在“修复”DNA突变。
• 青蛙实验表明，通过操纵生物电连接，即使是具有人类致癌基因的诱导肿瘤也可以被抑制或正常化。
• GBM或多形性胶质母细胞瘤（一种脑癌）是另一个应用实例，其中“关闭”这种生物电信号可以逆转癌症典型的“回滚”癌细胞活动，使它们恢复为正常功能背景下的“理想”状态作为身体多细胞功能的一部分。
• 在蝾螈和小鼠胚胎中观察到类似的癌细胞正常化，强调这是一种生物学可能性，而不仅仅是一个理论概念。
• 涡虫，凭借其混乱的基因组，表明完美的DNA不是强大的再生和癌症抵抗所必需的。它们的细胞已经进化到可以处理基因组噪声。
• 细胞决策不仅仅由遗传学驱动，而且是做出的。它们调整和修改其行为以应对环境压力源，包括化疗；它们表现出一种基本形式的智能（“基础认知”）。
• 生理性质（细胞如何记住要存在的模式）中存在问题，而不仅仅是DNA硬件问题。例如：镜像模式（例如，癫痫脑中的镜像效应）甚至心律失常和重新触发的心脏模式。

解决常见的误解

• 家族遗传易感性（硬件）：“保护硬件”。遗传的易感性与可能性有关。
• 虽然保持健康的DNA（避免损伤）是有益的，但这并不是全部。仅生物电中断就可能导致癌症。
• 年龄与癌症：再生和电通信能力的丧失增加导致癌症发生的几率增加。
• “离子通道药物”（电药物），通常已经用于癫痫等疾病，可以重新用于调节生物电信号，可能在全身水平上。这与靶向疗法或电击有很大不同。
• 对于成年人来说，药物益处（如影响离子通道的降压药）通常超过与生物电中断相关的任何理论风险。
• 然而，对于胚胎来说，服用某些生物电药物会受到影响。
• 肝脏可以再生（并做涡虫所做的事情）。人类可以再生指尖（非常末端、指尖的最远端部分，以及在人类生长早期阶段（儿童与成人））。