The need for new theoretical frameworks to understand bioelectric genotype-phenotype mapping and the emergent properties of multicellular bioelectric systems

The paper titled “Open Problems in Synthetic Multicellularity” addresses several key areas in the field of synthetic biology, specifically focusing on the challenges and opportunities in creating synthetic multicellular systems. Here are the main points discussed in the paper:

1. Introduction to Multicellularity:
   • Multicellularity represents a significant evolutionary transition that enabled the development of complex life forms.
   • The study of multicellularity combines experimental, comparative, and theoretical approaches, revealing insights into the mechanisms and evolutionary dynamics of multicellular systems.
2. Synthetic Multicellular Systems:
   • The paper categorizes synthetic multicellular systems into three main classes:
     1. Synthetic Multicellular Circuits: These involve engineering cellular circuits within living cells to perform computational tasks.
     2. Programmable Synthetic Assemblies: These systems use predictable properties of cellular adhesion and morphodynamics to create spatially organized cell assemblies.
     3. Synthetic Morphology and Agential Materials: This class includes organoids and biobots that exhibit emergent properties and behaviors not directly engineered at the genetic level.
3. Challenges and Open Problems:
   • The paper outlines several open problems in the field, including:
     • The design and scalability of synthetic developmental programs.
     • The integration of memory and learning in synthetic systems.
     • The exploration of synthetic collective intelligence and synthetic neural cognition.
     • The creation of synthetic proto-organisms and new organs.
     • The development of multiscale synthetic holobionts and synthetic behavior.
4. Theoretical and Practical Implications:
   • The paper emphasizes the importance of interdisciplinary approaches to address the complexities of multicellular systems.
   • It highlights the need for new theoretical frameworks to understand the genotype-phenotype mapping and the emergent properties of multicellular systems.
   • The potential applications of synthetic multicellular systems in medicine, bioengineering, and understanding evolutionary processes are discussed.
5. Conclusion:
   • The authors call for further research and collaboration to tackle the open problems and push the boundaries of what is possible in synthetic biology.
   • They emphasize the potential of synthetic multicellular systems to provide new insights into the principles of life and to develop novel biomedical and biotechnological applications.

In the context of synthetic multicellularity, bioelectricity plays a crucial role in the development and functioning of multicellular systems. Here’s how bioelectricity fits into the field based on the concepts presented in the paper “Open Problems in Synthetic Multicellularity”:

1. Regulation of Cellular Processes:
   • Bioelectricity refers to the electrical potentials and fields generated by cells, which can influence various cellular processes including growth, differentiation, and pattern formation.
   • It is involved in the regulation of gene expression and can affect the behavior of cells in a multicellular context, helping to coordinate activities across large cell populations.
2. Development and Morphogenesis:
   • During development, bioelectric signals are critical for the proper formation of tissues and organs. These signals guide cells to form complex structures through processes like cell migration, proliferation, and apoptosis.
   • Bioelectric gradients are essential for establishing body axes and for the spatial organization of cells, contributing to the emergence of complex multicellular patterns.
3. Self-Organization and Emergence:
   • Bioelectricity contributes to the self-organizing properties of multicellular systems. By creating and maintaining electrical gradients, cells can communicate and synchronize their activities, leading to the emergence of organized structures and functions.
   • Synthetic systems can leverage bioelectric signals to enhance the predictability and robustness of engineered multicellular assemblies.
4. Synthetic Bioelectric Circuits:
   • Synthetic biologists are exploring the use of bioelectric circuits to create programmable multicellular systems. By engineering cells to produce specific bioelectric signals, researchers can design synthetic tissues and organs with desired properties.
   • These bioelectric circuits can be used to control cell behavior in real-time, providing a powerful tool for developing advanced biobots and organoids.
5. Bioelectricity in Regeneration and Healing:
   • Bioelectricity is a key factor in tissue regeneration and healing. Synthetic multicellular systems can be designed to mimic natural bioelectric signals to promote regeneration and repair of damaged tissues.
   • This approach can lead to the development of advanced therapies for regenerative medicine, leveraging the body’s inherent bioelectric mechanisms to guide healing processes.
6. Agential Properties and Behavior:
   • The concept of cells and tissues as agential materials suggests that bioelectricity can endow synthetic multicellular systems with goal-directed behaviors. These systems can use bioelectric signals to adapt to their environment, solve problems, and perform complex tasks.
   • By harnessing the agential properties of bioelectricity, synthetic biologists can create more sophisticated and autonomous multicellular constructs.

In summary, bioelectricity is integral to synthetic multicellularity, providing a means to regulate and coordinate cellular activities, enhance self-organization, and create programmable and adaptive multicellular systems. This integration of bioelectric principles opens new avenues for research and applications in synthetic biology and regenerative medicine.

1. Bioelectric Fields as Fundamental to Life Processes: Burr’s research emphasized the importance of bioelectric fields in guiding growth, development, and healing within biological organisms. Similarly, the work by Ciaunica, Shmeleva, and Levin underscores the role of bioelectric phenomena in coupling neuronal and immune cellular processing, suggesting that cognitive processes and immune responses are deeply integrated and influenced by bioelectric signals within the human body. This parallels Burr’s idea that bioelectric patterns serve as blueprints for biological organization.
2. Interdisciplinary Approach: Burr was known for his interdisciplinary approach, integrating concepts from physics into biology to explore the electrical nature of life. The study “The brain is not mental!” follows in this tradition by bridging neuroscience, immunology, and bioelectric science. It highlights how the integration of different scientific disciplines can lead to a deeper understanding of complex biological phenomena, specifically the interplay between the brain, immune system, and bioelectric signals.
3. Health and Disease: Burr explored the potential of bioelectric fields in diagnosing and understanding diseases, notably cancer. The research by Ciaunica, Shmeleva, and Levin supports this line of inquiry by demonstrating how bioelectric interactions between neuronal and immune processes can influence health outcomes. Their work suggests that disruptions or modifications in these bioelectric signals could have implications for disease processes, aligning with Burr’s hypothesis that changes in bioelectric patterns can signal pathological states.
4. Regenerative Medicine and Developmental Biology: Burr’s work hinted at the potential applications of bioelectricity in promoting healing and regeneration. The findings of Ciaunica, Shmeleva, and Levin contribute to this area by providing evidence of the bioelectric basis of cognitive and immune interactions, which could have implications for regenerative medicine and developmental biology. Understanding how bioelectric fields influence the interaction between neuronal and immune systems could lead to novel therapeutic approaches that harness bioelectric signals for tissue regeneration and repair.
5. Philosophical Implications: Burr was also known for considering the philosophical implications of his work, challenging the traditional separation between mind and body. The study “The brain is not mental!” echoes this philosophical stance by arguing against a strict dichotomy between brain (mental) processes and bodily (immune) processes. Instead, it advocates for a holistic view where cognition is distributed across various cellular processes in the body, influenced by bioelectric signals. This supports Burr’s broader vision of life as an interconnected, bioelectrically mediated phenomenon.