The Regenerative Wisdom of The Body: Michael Levin

Summary

This talk explores the extraordinary regenerative and adaptive capabilities of living systems, from embryogenesis to advanced tissue regeneration. Key topics include how organisms self-assemble from a single cell, the role of bioelectricity in shaping growth and form, and how some animals, like salamanders and planaria, regenerate limbs and organs. The speaker highlights the potential of using these processes to treat birth defects, injuries, and even cancer. Additionally, the talk delves into the fascinating concept of cellular memory and the gap in understanding between genomics and anatomical development, suggesting new avenues for research in regenerative medicine.

Takeaways

• 😀 Embryonic development begins with a single cell, and it involves self-assembly into highly complex anatomical forms, raising questions about the origin of these patterns beyond genetic information.
• 😀 Embryogenesis is robust and flexible; for example, early mammalian embryos can regenerate into normal organisms when cut or combined, showing remarkable regenerative potential.
• 😀 Regeneration in animals like axolotls and planaria is a powerful process, allowing them to regenerate entire organs, including limbs and even parts of the brain, raising potential applications for human regenerative medicine.
• 😀 Planaria, which can regenerate from nearly any cut, show no aging, and even regenerate their brain and memories, suggesting that regeneration can be decoupled from aging processes in certain species.
• 😀 Salamanders and deer have the ability to regenerate their body parts, including highly complex structures like antlers, highlighting the potential for mammalian regenerative capabilities.
• 😀 Certain animals can regenerate or repair their bodies in a highly organized manner, even with chaotic genomes, demonstrating that structural patterning can be maintained despite genetic irregularities.
• 😀 The ability to regenerate in animals is linked to the presence of a special class of cells, like the neoblasts in planaria, which can propagate mutations but still produce normal regenerations.
• 😀 The process of anatomical surveillance, such as when a salamander’s tail remodels into a limb, suggests that cells can make decisions not only about their identity but also about how to fit into the body’s larger anatomical pattern.
• 😀 Primitive cognition exists at the cellular level; for example, the ability of tadpoles to process visual input from eyes placed on their tail highlights the brain’s remarkable plasticity in adapting to radically altered body plans.
• 😀 Bioelectric circuits play a fundamental role in cellular communication and patterning, controlling growth, form, and the behavior of tissues through electrical gradients, with potential implications for treating birth defects and cancer.
• 😀 The current state of the field suggests we still don’t fully understand how complex structures emerge from genetic and molecular signals, particularly the top-down control that directs cellular behavior toward specific anatomical outcomes.

Q & A

What is the main message of the sculpture by Ko Fukuda, and how does it relate to the talk?

The sculpture made of knives and forks symbolizes hidden patterns that are not immediately apparent. It represents the idea that complex patterns, like those in living systems, can only be understood when viewed in the appropriate way. This concept parallels the main theme of the talk about the hidden capabilities of living organisms, such as embryogenesis, regeneration, and plasticity.

How does embryogenesis demonstrate the concept of self-organization?

Embryogenesis showcases self-organization through the development of complex forms from a single fertilized cell. Regardless of the species—whether it's an elephant, an oak tree, or a jellyfish—the process reliably creates highly complex anatomical structures. This process doesn't just involve cell differentiation but also large-scale organization that is still not fully understood.

What is the difference between a teratoma and a properly developing embryo?

A teratoma is a tumor that contains mature tissues like skin, teeth, and bone, but it lacks the large-scale three-dimensional organization seen in a developing embryo. In contrast, an embryo not only differentiates into various cell types but also organizes those cells into a structured, functional anatomy, with organs and tissues placed in the correct relative positions.

What makes regeneration in salamanders and planaria so remarkable?

Salamanders, particularly axolotls, can regenerate entire limbs, jaws, portions of their brain, and other organs. Similarly, planaria, a type of flatworm, can regenerate entire bodies even from tiny fragments, including regenerating complex organs like the brain and nervous system. This regenerative capability raises important questions about how animals 'know' how to recreate missing structures with such precision.

What is the significance of the ability of planaria to regenerate from numerous pieces?

Planaria's ability to regenerate from up to 273 pieces is a remarkable example of biological plasticity. Each fragment regenerates the missing structures perfectly, which suggests that there is a remarkable level of coordination and patterning in their cells, despite having a 'messy' genome with mutations and varying chromosome numbers.

How does the regenerative ability of planaria challenge our understanding of genetics and inheritance?

Planaria's regenerative abilities challenge traditional genetic principles. Unlike most organisms, where only germline mutations are passed on to offspring, planaria can propagate mutations throughout their entire body, including to future generations. This process, which bypasses Weissman’s barrier (the concept that only genetic changes in germ cells are inherited), makes planaria unique in the study of genetics and regeneration.

How does the concept of anatomical surveillance apply to regeneration?

Anatomical surveillance refers to the process by which cells in a regenerative environment 'know' what the final structure should look like. For example, when a salamander's tail is surgically attached to a limb location, the tail cells start reorganizing into a limb, demonstrating that cells can understand the larger anatomical context and reprogram themselves to form the correct structure.

What role does bioelectricity play in the regulation of growth and development?

Bioelectricity plays a crucial role in regulating growth, form, and regeneration. Cells communicate electrically via voltage gradients, which help coordinate the development and repair of tissues. By manipulating these electrical signals, researchers can influence tissue patterning, as shown in experiments creating six-legged frogs, suggesting that bioelectricity can be harnessed to control biological processes like regeneration and cancer treatment.

How do memory and regeneration intersect in planaria?

In planaria, even after regenerating their brains, these organisms retain memories of tasks they were trained to do before the head was removed. This suggests that memories are not solely stored in the brain but are distributed throughout the body. This phenomenon raises important questions about the relationship between memory, regeneration, and the broader body structure.

What are some of the unresolved questions in the study of regenerative biology?

Several unresolved questions remain in regenerative biology, including how cells 'know' their position in the body and how they coordinate to regenerate complex structures. Additionally, while we understand many of the molecular mechanisms involved in regeneration, the 'algorithms' that guide these processes—how cells process and respond to information about their environment—are still largely unknown.