Introduction: Beyond the DNA-Centric Model

• The traditional view of DNA as the sole “software” of life leaves many biological mysteries unsolved, such as flexible development and regeneration.
• DNA mainly just decides the materials a cell contains.

The “Picasso Frog” Experiment

• Tadpoles with rearranged facial features (“Picasso frogs”) can still develop into relatively normal-looking frogs.
• This demonstrates that development is not a rigid, pre-programmed sequence of movements. Instead, it’s a flexible, goal-oriented process aiming to minimize the *error* between the current state and a “target morphology” (a correct frog face).
• This adaptive, error-correcting behavior is a form of biological intelligence, implying that cells cooperate and make decisions to achieve a specific anatomical outcome.

Bioelectricity: The “Software” Layer

• Cells communicate not only biochemically and physically, but also electrically. This “non-neural bioelectricity” exists in *all* cells, not just nerve cells.
• Electrical signals between cells form networks that process information and store “pattern memories,” similar to how brains store information. These memories include large-scale anatomical plans.
• By visualizing these electrical conversations (using voltage-sensitive dyes), we can see the “electrical software” running on top of the “cellular hardware” (defined by DNA).
• Bioelectricity directs cells when to decide left, right, head, tail and many more directions.

Analogy: Machine Code vs. High-Level Language

• Traditional biology often focuses on the “machine code” level (biochemical signals between individual cells), which is like trying to program a computer by directly manipulating its wires.
• Bioelectricity is like a “high-level language” that controls the *overall anatomical outcome* without needing to micromanage every cellular detail. Understanding this language gives us a powerful new way to influence development.
• If you can rewrite the electrical, then you may influence large body systems without interacting directly with DNA.

Planarian Regeneration and Rewriting the “Body Plan”

• Planarians (flatworms) are masters of regeneration, capable of regrowing any lost body part.
• There’s an electrical gradient (head-to-tail) in a planarian fragment that dictates where new heads and tails will form. This gradient can be manipulated.
• By altering this bioelectric gradient (by turning specific ion channels on or off – *not* by applying external electricity), researchers can create two-headed or no-headed planarians.
• Remarkably, two-headed worms *continue to regenerate as two-headed* even after both heads are cut off (with no genetic editing), showing that the “body plan” memory has been *permanently rewritten* and is stored bioelectrically, not just in DNA.
• The bioelectrical field stores anatomical “what to do’s” and may be used to rewrite memory.
• This demonstrates a form of *non-genetic* memory – a stable, rewritable pattern that influences future regeneration.

Beyond Planaria: Inducing Organ Growth

• By manipulating ion channels in tadpoles, researchers can induce the growth of ectopic (extra) eyes in locations where eyes don’t normally form.
• These induced eyes are complete and functional (with lens, retina, optic nerve), showing that the *body already knows how to build complex organs*. The bioelectric signals trigger existing “subroutines.”
• Researchers are figuring out how to make limbs and hearts.

Xenobots: Novel Life Forms from Frog Skin Cells

• Xenobots are created by isolating frog skin cells and allowing them to self-assemble.
• These cells, genetically identical to normal frog cells, spontaneously form *new* organisms with unique behaviors (movement, navigation, maze running), distinct from tadpoles or frogs. This shows how cells will find some type of structure when constraints are changed or removed.
• Frog skin cells use their cilia (normally used for moving mucus) to *swim*, demonstrating how cells can *repurpose* their existing “hardware” for new functions.
• Xenobots will create spontaneous and “unprogrammed” behaviors.
• AI (in collaboration with Josh Bongard) can model and evolve xenobot designs *in silico* (on a computer) before they are built in the lab. This highlights the incredible plasticity of cells.
• Researchers used computers to build the evolutionary tree/history of xenobots, when it never exisited before, meaning a lifeform/body that has a history outside Earth and created by pure modeling.

Implications and Future Directions

• **Regenerative Medicine:** Cracking the bioelectric code could enable us to regenerate limbs, organs, and correct birth defects by rewriting the “target morphology” that cells strive for.
• They are able to fix traumatic injury in frogs and other life, potentially stopping the cause of cancer, fixing aging and degenrative issues in animals.
• **Tumor Normalization:** Cancers could potentially be “normalized” by influencing the bioelectric signals that control cell behavior and tissue organization.
• **Broader Understanding of Intelligence:** Bioelectricity highlights that biological intelligence exists *before* the evolution of brains, suggesting new avenues for AI and machine learning based on how *body cells*, not just brain cells, solve problems.
• Researchers want to find way to communicate to large body systems with large signals/blueprints and *not* in detail through each individual.

引言：超越以DNA为中心的模型

• 传统的将DNA视为生命唯一“软件”的观点无法解释许多生物学谜团，例如发育的灵活性和再生能力。
• DNA 主要决定细胞所包含的物质。

“毕加索青蛙”实验

• 面部特征被重新排列的蝌蚪（“毕加索青蛙”）仍然可以发育成外观相对正常的青蛙。
• 这表明发育不是一个僵化的、预先编程的运动序列。相反，它是一个灵活的、目标导向的过程，旨在最小化当前状态和“目标形态”（正确的青蛙脸）之间的*误差*。
• 这种适应性的、纠正错误的行为是一种生物智能的形式，这意味着细胞合作并做出决定以实现特定的解剖结果。

生物电：“软件”层

• 细胞不仅通过生物化学和物理方式进行通讯，还通过电进行通讯。这种“非神经生物电”存在于*所有*细胞中，而不仅仅是神经细胞。
• 细胞之间的电信号形成处理信息和存储“模式记忆”的网络，类似于大脑存储信息的方式。这些记忆包括大规模的解剖蓝图。
• 通过可视化这些电对话（使用电压敏感染料），我们可以看到运行在“细胞硬件”（由DNA定义）之上的“电软件”。
• 生物电指导细胞何时决定左、右、头、尾和更多方向。

类比：机器码与高级语言

• 传统的生物学通常关注“机器码”级别（单个细胞之间的生物化学信号），这就像试图通过直接操纵计算机的电线来编程一样。
• 生物电就像一种“高级语言”，它控制*整体解剖结果*，而不需要微观管理每个细胞的细节。理解这种语言为我们提供了一种强大的影响发育的新方法。
• 如果你可以重写电信号，那么你可能会影响大的身体系统，而无需直接与DNA交互。

涡虫再生和重写“身体蓝图”

• 涡虫（扁虫）是再生大师，能够再生任何失去的身体部位。
• 涡虫片段中存在电梯度（头到尾），决定了新头部和尾巴形成的位置。这个梯度可以被操纵。
• 通过改变这种生物电梯度（通过打开或关闭特定的离子通道——*而不是*施加外部电流），研究人员可以创造出双头或无头的涡虫。
• 值得注意的是，即使在两个头部都被切断后（没有基因编辑），双头涡虫*仍然继续再生为双头*，这表明“身体蓝图”记忆已被*永久重写*，并且是生物电存储的，而不仅仅是在DNA中。
• 生物电场存储解剖结构的“该做什么”，并可用于重写记忆。
• 这证明了一种*非遗传*记忆的形式——一种影响未来再生的稳定的、可重写的模式。

超越涡虫：诱导器官生长

• 通过操纵蝌蚪中的离子通道，研究人员可以在通常不形成眼睛的位置诱导异位（额外的）眼睛的生长。
• 这些诱导的眼睛是完整且具有功能的（具有晶状体、视网膜、视神经），表明*身体已经知道如何构建复杂的器官*。生物电信号触发现有的“子程序”。
• 研究人员正在研究如何制造四肢和心脏。

异种机器人：来自青蛙皮肤细胞的新生命形式

• 异种机器人是通过分离青蛙皮肤细胞并允许它们自组装而产生的。
• 这些细胞在基因上与正常的青蛙细胞相同，自发地形成*新的*生物体，具有独特的行为（运动、导航、迷宫奔跑），与蝌蚪或青蛙不同。这表明当约束条件改变或移除时，细胞将如何找到某种类型的结构。
• 青蛙皮肤细胞利用它们的纤毛（通常用于移动粘液）来*游泳*，这表明细胞如何可以*重新利用*它们现有的“硬件”来实现新功能。
• 异种机器人会产生自发的和“未编程”的行为。
• 人工智能（与 Josh Bongard 合作）可以在实验室构建异种机器人之前，在*计算机上（in silico）*对异种机器人设计进行建模和演化。这突出了细胞惊人的可塑性。
• 研究人员使用计算机构建了异种机器人的进化树/历史，而它以前从未存在过，这意味着一个生命形式/身体在地球之外有一个历史，并且是由纯粹的建模创造的。

影响和未来方向

• **再生医学：**破解生物电密码可以使我们能够通过重写细胞努力实现的“目标形态”来再生四肢、器官和纠正出生缺陷。
• 他们能够修复青蛙和其他生物的创伤性损伤，有可能阻止癌症的发生，修复动物的衰老和退化问题。
• **肿瘤正常化：**癌症有可能通过影响控制细胞行为和组织组织的生物电信号而被“正常化”。
• **对智能的更广泛理解：**生物电强调生物智能存在于大脑进化*之前*，这为基于*身体细胞*（而不仅仅是大脑细胞）解决问题的人工智能和机器学习提供了新的途径。
• 研究人员希望找到一种方法，用大型信号/蓝图与大型身体系统进行沟通，而不是通过每个个体进行详细沟通。