Michael Levin Bioelectricity 101 Crash Course Lesson 29: Xenobots: Exploring New Forms of Life with Bioelectricity Summary

• Xenobots are small (sub-millimeter), self-propelled biological constructs made entirely from frog (Xenopus laevis) embryonic cells.
• They are not genetically modified organisms (GMOs). They use the normal genes of the frog, but those genes are expressed in a completely new context, resulting in novel structures and behaviors.
• Xenobots are created using a bottom-up approach, exploiting the inherent self-organizing abilities of cells. They are not built piece-by-piece, but rather arise from the interactions of cells liberated from their normal developmental constraints.
• Xenobots move using cilia on their surface, normally used by frog skin cells to clear debris. This is a prime example of repurposing existing biological machinery.
• They exhibit emergent behaviors, including diverse movement patterns, self-repair, and collective particle aggregation.
• Xenobots have a limited lifespan and are biodegradable, making them potentially safer for environmental applications than artificial robots.
• Computational models can be used to understand and predict Xenobot behavior, and even to design new Xenobot forms with enhanced capabilities.
• Xenobots demonstrate that novel, functional forms of life can be created without direct genetic manipulation, challenging our understanding of what’s possible in biology. They represent “liberated cells” free to realize capacities latent within all cells.
• Although xenobots use normal (wild-type) frog cells and their intrinsic behaviours, they are fundamentally distinct in arrangement.
• They provide proof of a new model of designing machines: allow biological components to self-assemble with a goal/purpose given.
• The core concept of basal cognition (simple organisms making decisions) has high application to explain and interpret their behaviours.

Michael Levin Bioelectricity 101 Crash Course Lesson 29: Xenobots: Exploring New Forms of Life with Bioelectricity

Up to this point, we’ve explored bioelectricity as a fundamental force shaping development, regeneration, and cellular behavior within the normal context of an organism’s body plan. We’ve seen how bioelectric signals guide the formation of organs, control wound healing, and even influence the behavior of individual cells. But what happens when we take cells out of their normal context, free them from the usual constraints of the embryo, and allow them to self-organize? The answer, as demonstrated by the creation of Xenobots, is truly remarkable.

Xenobots are tiny (less than a millimeter), living machines created entirely from the cells of the African clawed frog, Xenopus laevis. It’s crucial to understand that Xenobots are not genetically modified. They use the same genes as a normal frog. What’s different is the context. The cells are taken from a very early stage of development (the blastula stage) and placed in a new environment, where they’re allowed to interact and self-organize without the usual signals and constraints of the developing embryo. It’s like taking a group of construction workers and giving them a pile of building materials, but without any blueprints. They’ll still build something, but it won’t be a standard house. It will be something new, based on their inherent abilities and the interactions between the materials.

The process of creating Xenobots starts with explants – small pieces of tissue taken from the animal cap region of the early frog embryo. This region is normally destined to become skin. These explants are then placed in a simple saline solution. Without the usual signals from the rest of the embryo, the cells in these explants do something amazing: they self-organize. They don’t form a miniature frog, or even a recognizable piece of frog tissue. Instead, they form a small, spheroidal structure – the Xenobot. This self-organization is key, a spontaneous development, bottom up.

One of the most striking features of Xenobots is their ability to move. They don’t have muscles or legs. Instead, they use cilia – tiny, hair-like structures on their surface – to propel themselves through the water. These cilia are the same cilia that are normally found on the skin of frog embryos and tadpoles, where they help to sweep away mucus, debris, and pathogens. In the Xenobots, this existing cellular machinery is repurposed for locomotion. This is a perfect example of how biology can repurpose existing structures and functionalities for a wide range and ability of capabilities.

Xenobots don’t all move in the same way. Some move in straight lines, others in circles, and some just kind of wiggle around. This diversity of movement patterns arises from the way the cilia are arranged and how they beat, which is itself a result of the self-organization process. This variety of behaviors becomes especially evident when large tracking, across long periods of times, show their differences, and can transition through various ‘movement states.’

But it’s not just about individual movement. When multiple Xenobots are placed together, they exhibit emergent behaviors. One of the most striking examples is their ability to aggregate particles. If you put Xenobots in an environment with small particles (like iron oxide beads), they will spontaneously push these particles together into piles. This isn’t something that was specifically programmed into them; it emerges from the interactions of the individual Xenobots and their movement patterns.

Another remarkable feature of Xenobots is their ability to self-repair. If you cut a Xenobot, it will heal the wound within minutes, re-forming its original shape. This is a testament to the inherent robustness and plasticity of living tissues. The shape itself emerges: It is not regeneration, as it does not revert into the standard “tadpole” format! The shape “choice” arises from bioelectric and biophysical gradients.

Xenobots also have a limited lifespan. They live for about a week to 10 days in a simple saline solution, powered by the yolk reserves from the original embryonic cells. After that, they naturally biodegrade. This is a significant advantage for potential applications, as it means they won’t persist indefinitely in the environment. Their lifespans can be increased however; if placed in the right nutrients, the xenobots will survive for much longer time scales, such as multiple months.

Now, let’s connect this back to bioelectricity. While Xenobots don’t have a nervous system (and experiments have explicitly shown that no neurons form on their surface of interiors), their behavior is undoubtedly influenced by bioelectric signals. Here’s how:

• Cilia and Membrane Potential: The beating of cilia is controlled by changes in membrane potential. The flow of ions across the cell membrane creates electrical signals that regulate the activity of the proteins that control ciliary movement.
• Cell-Cell Communication: The cells within a Xenobot are connected by gap junctions, which allow ions and small molecules to pass directly between them. This means that bioelectric signals can spread from cell to cell, coordinating their activity. This is the basis of multicellular “computation”.
• Morphogen Distribution: As we’ve learned, microtubules (part of the cytoskeleton) play a crucial role in transporting materials within cells, including ion channels. The organization of the cytoskeleton within Xenobots can influence the distribution of ion channels, and therefore the pattern of bioelectric activity.

While the direct manipulation of bioelectric signals hasn’t been the primary focus of *all* Xenobot research to date (though much has indeed focused on bioelectricity), it’s clear that bioelectricity is playing a crucial, underlying role in their self-organization, movement, and behavior. Future research will undoubtedly explore how manipulating bioelectric signals can be used to control and enhance Xenobot capabilities.

One of the most exciting aspects of Xenobot research is the use of computational models. Researchers have created computer simulations of Xenobots, using simplified models of their shape, ciliary movement, and interactions with the environment. These models allow them to:

• Understand Emergent Behavior: The models can help to explain how the simple interactions of individual Xenobots lead to complex collective behaviors, like particle aggregation.
• Predict Xenobot Behavior: The models can be used to predict how Xenobots will behave in different environments or with different properties.
• Design New Xenobots: Perhaps most excitingly, the models can be used to design new Xenobot forms with enhanced capabilities. For example, researchers have used evolutionary algorithms to find Xenobot shapes that are particularly good at gathering particles.

This combination of biological experimentation and computational modeling is a powerful approach for exploring the potential of synthetic living machines.

What are the broader implications of Xenobots?

• New Forms of Life: Xenobots demonstrate that it’s possible to create novel, functional forms of life without directly altering the genetic code. This challenges our traditional understanding of what constitutes an “organism” and opens up new possibilities for synthetic biology.
• Basal Cognition: Xenobots, despite lacking a nervous system, exhibit surprisingly complex behaviors. This suggests that even simple collections of cells can exhibit a form of “basal cognition” – the ability to sense their environment, make decisions, and adapt their behavior. The paper shows that these cells and aggregations, display capabilities unexpected, given the simplicity and the source of the materials (embryotic tissue that otherwise make skin).
• Applications: Xenobots have potential applications in:
  • Environmental remediation: Cleaning up pollutants or microplastics.
  • Drug delivery: Delivering drugs to specific locations in the body.
  • Biomedical research: Studying fundamental biological processes like self-organization and collective behavior.

Xenobots represent a new frontier in biology and robotics. They are a testament to the remarkable plasticity and adaptability of living cells, and they offer a glimpse into a future where we can design and build living machines with diverse forms and functions. They also, and very profoundly, highlight and reveal fundamental properites about life: Xenobots display self-motivated actions and purpose.

Michael Levin Bioelectricity 101 Crash Course Lesson 29: Xenobots: Exploring New Forms of Life with Bioelectricity Quiz

1. What are Xenobots primarily made of?

A) Synthetic materials like plastic and metal
B) Genetically modified bacteria
C) Cells from Xenopus laevis frog embryos
D) Stem cells from adult humans

2. Are Xenobots genetically modified organisms (GMOs)?

A) Yes, their genes are extensively altered.
B) No, they use the normal genes of the frog.
C) Only some Xenobots are GMOs.
D) It is unknown whether they are GMOs.

3. How are Xenobots created?

A) By 3D-printing synthetic materials.
B) By carefully assembling individual cells.
C) By allowing cells from frog embryos to self-organize.
D) By injecting adult frog cells with special chemicals.

4. What structures do Xenobots use to move?

A) Muscles
B) Legs
C) Cilia
D) Flagella

5. What is the normal function of the cilia used by Xenobots?

A) To propel the frog through water.
B) To sense light.
C) To clear debris from the frog’s skin.
D) To help the frog breathe.

6. Which of the following is an example of an emergent behavior exhibited by Xenobots?

A) Moving in a straight line.
B) Aggregating particles into piles.
C) Responding to light.
D) Self-repairing damage.

7. What is a key advantage of Xenobots over traditional robots in terms of environmental impact?

A) They are stronger and more durable.
B) They are faster and more efficient.
C) They are biodegradable.
D) They can be controlled remotely.

8. What computational technique can be used to design new Xenobot shapes?

A) Linear regression
B) Evolutionary algorithms
C) K-means clustering
D) Principal component analysis

9. True/False: Scientists created explicit and direct shapes by hand that were later adopted into “living” form by xenobots.

A) True
B) False

10. Xenobots use tissue, in their construction, that otherwise would go to making…

A) Nerves.
B) Heart
C) Skin.
D) Gut.

11. True/False: Xenobots, once constructed, can heal/repair damage.

A) True
B) False.

12. Xenobots provide a new way to potentially solve challenges such as:

A) Contaminant collection.
B) Biomedicine challenges.
C) Understanding the “bottom-up” construction.
D) All of the Above

13. Which of the following is not a potential application of Xenobots?

A) Cleaning up pollution
B) Delivering drugs inside the body
C) Building houses
D) Studying self-organization

14. Xenobots demonstrate that novel forms of life can be created without:

A) Using living cells
B) Direct genetic modification
C) Using computer simulations
D) Any human intervention

15. What is meant by “basal cognition,” a process highlighted with xenobots.

A) Brain activity
B) The most simplest kinds of behaviour, with only instinct.
C) Complex behaviour generated even without traditional brains.
D) How cells think

16. The normal function of Xenopus cells used in constructing the Xenobot have _____ role in bioelectricity

A) no
B) an important, and exploitable

17. When scientists performed mechanical damage on a Xenobot, did it:

A) Regenerate
B) Repair, back into its xenobot-structure
C) Repair, back into its frog original configuration.
D) B and C

18. True/False: The normal wild type frog genes were changed or edited to produce Xenobots.

A) True
B) False

19. Xenobots have:

A) Lots of Neurons
B) Only a few neurons.
C) No neurons, ever
D) Unknown

20. The philosophical point(s) that Michael Levin wishes to highlight is/are that:

A) Standard evolutionary processes result in the creation of many diverse types of organisms, each exhibiting specialized skills.
B) All cells, freed of certain contextual limitations, can result in new arrangements or types of functionality not normally found in those cells.
C) Bioelectricity can help inform future development, of better medicines and robotics.
D) All of the Above

Michael Levin Bioelectricity 101 Crash Course Lesson 29: Xenobots: Exploring New Forms of Life with Bioelectricity Answer Sheet

1. C

2. B

3. C

4. C

5. C

6. B

7. C

8. B

9. B

10. C

11. A

12. D

13. C

14. B

15. C

16. B

17. B

18. B

19. C

20. D

迈克尔·莱文 生物电 101 速成课程 第29课：Xenobots：探索生物电创造的新生命形式 摘要

• Xenobots 是微小的（亚毫米级）、自推进的生物结构，完全由非洲爪蟾 (Xenopus laevis) 胚胎细胞制成。
• 它们不是转基因生物 (GMO)。 它们使用青蛙的正常基因，但这些基因在全新的环境中表达，从而产生新的结构和行为。
• Xenobots 是使用自下而上的方法创建的，利用了细胞固有的自组织能力。 它们不是逐块构建的，而是由摆脱了正常发育限制的细胞相互作用产生的。
• Xenobots 使用其表面的纤毛移动，这些纤毛通常被青蛙皮肤细胞用来清除碎屑。 这是重新利用现有生物机制的典型例子。
• 它们表现出涌现行为，包括多样化的运动模式、自我修复和集体颗粒聚集。
• Xenobots 的寿命有限且可生物降解，这使得它们在环境应用中可能比人造机器人更安全。
• 计算模型可用于理解和预测 Xenobot 行为，甚至可以设计具有增强功能的新 Xenobot 形式。
• Xenobots 证明无需直接基因操作即可创造出新颖、功能性的生命形式，挑战了我们对生物学中可能性的理解。 它们代表“解放的细胞”，可以自由地实现所有细胞中潜在的能力。
• 虽然 xenobots 使用正常的（野生型）青蛙细胞及其内在行为，但它们在排列上根本不同。
• 它们为设计机器的新模型提供了证据：允许生物组件在给定的目标/目的下自组装。
• 基础认知（简单生物做出决策）的核心概念对其行为的解释和解读具有很高的适用性。

迈克尔·莱文 生物电 101 速成课程 第29课：Xenobots：探索生物电创造的新生命形式

到目前为止，在本课程中，我们已经探索了生物电作为塑造正常生物体身体结构内发育、再生和细胞行为的基本力量。 我们已经看到生物电信号如何引导器官形成、控制伤口愈合，甚至影响单个细胞的行为。 但是，如果我们将细胞脱离其正常环境，摆脱胚胎的通常约束，并允许它们自组织，会发生什么？ 正如 Xenobots 的创造所证明的那样，答案确实非常了不起。

Xenobots 是微小的（小于一毫米）、活的机器，完全由非洲爪蟾 (Xenopus laevis) 的细胞制成。 重要的是要明白 Xenobots 不是转基因生物。 它们使用与正常青蛙相同的基因。 不同的是环境。 细胞取自发育的早期阶段（囊胚阶段）并放置在新环境中，在那里它们可以在没有发育中胚胎的通常信号和约束的情况下相互作用和自组织。 这就像带一群建筑工人给他们一堆建筑材料，但没有任何蓝图。 他们仍然会建造一些东西，但它不会是标准的房子。 它将是基于其固有能力和材料之间相互作用的新东西。

创建 Xenobots 的过程始于外植体——从早期青蛙胚胎的动物帽区域取出的小块组织。 该区域通常注定要变成皮肤。 然后将这些外植体放入简单的盐溶液中。 在没有来自胚胎其余部分的通常信号的情况下，这些外植体中的细胞会做一些惊人的事情：它们会自组织。 它们不会形成微型青蛙，甚至不会形成可识别的青蛙组织块。 相反，它们形成了一个小的球状结构——Xenobot。 这种自组织是关键，是自发发育，自下而上。

Xenobots 最显著的特征之一是它们的移动能力。 它们没有肌肉或腿。 相反，它们使用纤毛——其表面的微小毛发状结构——来推动自己在水中前进。 这些纤毛与通常在青蛙胚胎和蝌蚪皮肤上发现的纤毛相同，它们有助于清除粘液、碎屑和病原体。 在 Xenobots 中，这种现有的细胞机制被重新利用于运动。 这是生物学如何将现有结构和功能重新用于广泛范围和能力的一个完美例子。

Xenobots 并非都以相同的方式移动。 有些沿直线移动，有些沿圆形移动，有些只是四处摆动。 这种运动模式的多样性源于纤毛的排列方式和它们的跳动方式，这本身就是自组织过程的结果。 当进行长时间的大范围跟踪时, 这种多样化的行为变得尤其明显，显示出它们的差异, 并且可以在各种“运动状态”之间转换。

但这不仅仅是关于个体运动。 当多个 Xenobots 放在一起时，它们会表现出涌现行为。 最显著的例子之一是它们聚集颗粒的能力。 如果你把 Xenobots 放在有小颗粒（如氧化铁珠）的环境中，它们会自发地将这些颗粒推到一起成堆。 这不是专门编程到它们中的东西； 它源于单个 Xenobots 及其运动模式的相互作用。

Xenobots 的另一个显著特征是它们的自我修复能力。 如果你切开一个 Xenobot，它会在几分钟内愈合伤口，重新形成其原始形状。 这是生命组织固有的稳健性和可塑性的证明。形状本身出现了：它不是再生，因为它不会恢复到标准的“蝌蚪”形态！ 形状“选择”来自生物电和生物物理梯度。

Xenobots 也有有限的寿命。 它们在简单的盐溶液中存活大约一周到 10 天，由原始胚胎细胞中的卵黄储备提供能量。 在那之后，它们会自然地生物降解。 这对于潜在应用来说是一个显著的优势，因为这意味着它们不会无限期地存在于环境中。 然而，它们的寿命可以延长； 如果放置在正确的营养物质中，xenobots 将存活更长的时间，例如多个月。

现在，让我们把这与生物电联系起来。 虽然 Xenobots 没有神经系统（实验明确表明它们的表面或内部没有形成神经元），但它们的行为无疑受到生物电信号的影响。 以下是原因：

• 纤毛和膜电位： 纤毛的跳动受膜电位变化的控制。 跨细胞膜的离子流会产生电信号，调节控制纤毛运动的蛋白质的活性。
• 细胞间通讯： Xenobot 内的细胞通过间隙连接连接，允许离子和小分子在它们之间直接传递。 这意味着生物电信号可以在细胞之间传播，协调它们的活动。 这是多细胞“计算”的基础。
• 形态发生素分布： 正如我们所了解的，微管（细胞骨架的一部分）在细胞内运输物质（包括离子通道）方面起着至关重要的作用。 Xenobots 内细胞骨架的组织会影响离子通道的分布，从而影响生物电活动的模式。

虽然生物电信号的直接操纵并不是所有 Xenobot 研究的重点（尽管许多研究确实关注生物电），但很明显，生物电在其自组织、运动和行为中起着至关重要的基础作用。 未来的研究无疑将探索如何操纵生物电信号来控制和增强 Xenobot 的能力。

Xenobot 研究最令人兴奋的方面之一是计算模型的使用。 研究人员使用 Xenobots 的形状、纤毛运动和与环境相互作用的简化模型创建了 Xenobots 的计算机模拟。 这些模型使他们能够：

• 理解涌现行为： 这些模型可以帮助解释单个 Xenobots 的简单交互如何导致复杂的集体行为，如粒子聚合。
• 预测 Xenobot 行为： 这些模型可用于预测 Xenobots 在不同环境或具有不同属性下的行为方式。
• 设计新的 Xenobots： 也许最令人兴奋的是，这些模型可以用来设计具有增强功能的新 Xenobot 形式。 例如，研究人员已经使用进化算法来寻找特别擅长收集颗粒的 Xenobot 形状。

这种生物实验和计算建模的结合是探索合成活体机器潜力的一种强大方法。

Xenobots 有哪些更广泛的含义？

• 新生命形式： Xenobots 证明无需直接改变遗传密码即可创造新颖、功能性的生命形式。 这挑战了我们对“有机体”构成的传统理解，并为合成生物学开辟了新的可能性。
• 基础认知： Xenobots 尽管没有神经系统，却表现出令人惊讶的复杂行为。 这表明，即使是简单的细胞集合也能表现出一种“基础认知”——感知环境、做出决策和适应行为的能力。 该论文表明，这些细胞和聚集体表现出意想不到的能力，考虑到简单性和材料的来源（原本会形成皮肤的胚胎组织）。
• 应用： Xenobots 在以下方面具有潜在应用：
  • 环境修复： 清理污染物或微塑料。
  • 药物输送： 将药物输送到体内的特定位置。
  • 生物医学研究： 研究自组织和集体行为等基本生物过程。

Xenobots 代表了生物学和机器人学的一个新前沿。 它们证明了活细胞非凡的可塑性和适应性，它们让我们瞥见了未来，我们可以设计和制造具有不同形式和功能的活体机器。 它们也模糊了生物学、机器人学和计算机科学之间的界限，为生命的本质和计算提供了新的视角。它提供了一种进行生物科学的途径，即解放“正常生物”的部分，看看它们在通常的结构/限制之外的行为方式。 它允许研究自组装和涌现等特性，以及在进化、复杂的生物体中（实际上）很难研究的basal(非神经)决策。

迈克尔·莱文 生物电 101 速成课程 第29课：Xenobots：探索生物电创造的新生命形式 小测验

1. Xenobots 主要由什么制成？

A) 塑料和金属等合成材料
B) 转基因细菌
C) 非洲爪蟾 (Xenopus laevis) 胚胎细胞
D) 成人干细胞

2. Xenobots 是转基因生物 (GMO) 吗？

A) 是的，它们的基因被广泛改变。
B) 不，它们使用青蛙的正常基因。
C) 只有一些 Xenobots 是 GMO。
D) 不知道它们是不是 GMO。

3. Xenobots 是如何创建的？

A) 通过 3D 打印合成材料。
B) 通过仔细组装单个细胞。
C) 通过让青蛙胚胎中的细胞自组织。
D) 通过向成年青蛙细胞注射特殊化学物质。

4. Xenobots 使用什么结构来移动？

A) 肌肉
B) 腿
C) 纤毛
D) 鞭毛

5. Xenobots 使用的纤毛的正常功能是什么？

A) 推动青蛙在水中前进。
B) 感知光线。
C) 清除青蛙皮肤上的碎屑。
D) 帮助青蛙呼吸。

6. 以下哪一项是 Xenobots 表现出的涌现行为的例子？

A) 沿直线移动。
B) 将颗粒聚集成堆。
C) 对光做出反应。
D) 自我修复损伤。

7. 就环境影响而言，Xenobots 相对于传统机器人的一个主要优势是什么？

A) 它们更强壮、更耐用。
B) 它们更快、更高效。
C) 它们可生物降解。
D) 它们可以远程控制。

8. 什么计算技术可以用来设计新的 Xenobot 形状？

A) 线性回归
B) 进化算法
C) K 均值聚类
D) 主成分分析

9. 对/错：科学家通过手工创建明确和直接的形状，然后被 xenobots 采用为“活体”形式。

A) 对
B) 错

10. Xenobots 在其结构中使用的组织，原本会形成…

A) 神经。
B) 心脏
C) 皮肤.
D) 肠道。

11. 对/错：Xenobots 一旦构建完成，就可以治愈/修复损伤。

A) 对
B) 错。

12. Xenobots 提供了一种新方法来潜在地解决以下挑战：

A) 污染物收集。
B) 生物医学挑战。
C) 理解“自下而上”的构建。
D) 以上都是

13. 以下哪一项不是 Xenobots 的潜在应用？

A) 清理污染
B) 在体内输送药物
C) 建造房屋
D) 研究自组织

14. Xenobots 表明无需以下操作即可创造出新颖的生命形式：

A) 使用活细胞
B) 直接基因改造
C) 使用计算机模拟
D) 任何人为干预

15. “基础认知”是什么意思，这是用 xenobots 突出显示的一个过程。

A) 大脑活动
B) 最简单的行为类型，只有本能。
C) 即使没有传统大脑也会产生的复杂行为.
D) 细胞如何思考

16. 用于构建 Xenobot 的爪蟾细胞的正常功能在生物电中起 _____ 作用

A) 没有
B) 重要的，并且可利用的

17. 当科学家对 Xenobot 进行机械损伤时，它会：

A) 再生
B) 修复，恢复到其 xenobot 结构
C) 修复，恢复到其青蛙原始形态。
D) B 和 C

18. 对/错：用于生产 Xenobots 的正常野生型青蛙基因被改变或编辑。

A) 对
B) 错

19. Xenobots 有：

A) 很多神经元
B) 只有几个神经元。
C) 从来没有神经元
D) 未知

20. 迈克尔·莱文希望强调的哲学观点是：

A) 标准的进化过程导致了许多不同类型的生物的产生，每种生物都表现出专门的技能。
B) 所有细胞，摆脱了某些环境限制，都可以产生这些细胞通常不具备的新排列或功能类型。
C) 生物电可以帮助未来的发展，提供更好的药物和机器人技术。
D) 以上都是

迈克尔·莱文 生物电 101 速成课程 第29课：Xenobots：探索生物电创造的新生命形式 答案表

1. C

2. B

3. C

4. C

5. C

6. B

7. C

8. B

9. B

10. C

11. A

12. D

13. C

14. B

15. C

16. B

17. B

18. B

19. C

20. D