Life and death are typically seen as stark opposites. However, the emergence of new multicellular life forms from the cells of a deceased organism introduces a fascinating “third state” that transcends these traditional boundaries.
Generally, death is defined as the irreversible cessation of an organism’s overall functioning. Yet, practices like organ donation demonstrate that organs, tissues, and cells can continue to operate even after the organism’s demise. This remarkable resilience raises an intriguing question: What mechanisms enable certain cells to persist and function post-mortem? and a bigger question, are we still alive or dead after we died as our cells or organs might continue to live?
Researchers delving into post-mortem phenomena have uncovered groundbreaking findings. Their recent review highlights how specific cells, when supplied with nutrients, oxygen, bioelectric signals, or biochemical cues, can transform into multicellular entities exhibiting new functions after death.
The concept of the third state challenges conventional views on cellular behaviour. While transformations such as caterpillars becoming butterflies or tadpoles evolving into frogs are well-known developmental processes, instances where organisms change in non-predetermined ways are scarce. Tumours, organoids, and perpetually dividing cell lines like HeLa cells used in the lab don’t fit into the third state as they do not develop new functions.
However, scientists discovered that skin cells from deceased frog embryos could adapt to laboratory conditions, reorganising into multicellular organisms known as xenobots. These xenobots exhibit behaviours far beyond their original biological roles. Specifically, they use cilia—tiny hair-like structures—for navigation and movement, whereas in living frog embryos, cilia primarily move mucus.
Xenobots can move, heal, and interact with their environment autonomously. They also perform kinematic self-replication, replicating their structure and function without growing—a stark contrast to more common replication methods involving growth within or on the organism’s body.
Further research revealed that isolated human lung cells could self-assemble into miniature multicellular organisms called anthrobots. These anthrobots exhibit novel behaviours and structures. They navigate their surroundings and can repair themselves and nearby injured neuron cells.
These findings underscore the inherent plasticity of cellular systems, challenging the notion that cells and organisms evolve only in predetermined ways. The third state suggests that organismal death may significantly influence life’s transformation over time.
Several factors determine whether cells and tissues can survive and function post-mortem. Environmental conditions, metabolic activity, and preservation techniques play crucial roles.
Different cell types have varying survival times. In humans, white blood cells die between 60 and 86 hours post-mortem. In mice, skeletal muscle cells can be regrown 14 days post-mortem, while fibroblast cells from sheep and goats can be cultured up to a month post-mortem.
Metabolic activity significantly impacts cell survival and function. Cells requiring continuous and substantial energy are harder to culture than those with lower energy needs. Preservation techniques like cryopreservation enable tissue samples such as bone marrow to function comparably to living donor sources.
Inherent survival mechanisms also influence cell and tissue longevity post-mortem. Researchers observed increased activity of stress-related and immune-related genes after organismal death, likely compensating for homeostasis loss. Factors like trauma, infection, and time since death also affect tissue and cell viability.
Variables such as age, health, sex, and species type further shape the post-mortem landscape. This complexity is evident in challenges faced when culturing and transplanting metabolically active islet cells from donors to recipients. Researchers believe autoimmune processes, high energy demands, and degradation of protective mechanisms contribute to many islet transplant failures.
The interplay of these variables and how they allow certain cells to function after an organism’s death remains unclear. One hypothesis posits that specialised channels and pumps in cell membranes act as intricate electrical circuits. These channels and pumps generate electrical signals enabling cell communication and specific functions like growth and movement, shaping the organism’s structure.
The extent to which different cell types can transform post-mortem is also uncertain. Previous research indicates that stress-related, immune-related, and epigenetic regulation genes activate after death in mice, zebrafish, and humans, suggesting widespread transformation potential among diverse cell types.
The third state offers new insights into cellular adaptability and potential medical applications. For instance, anthrobots derived from an individual’s living tissue could deliver drugs without triggering immune responses. Engineered anthrobots injected into the body might dissolve arterial plaque in atherosclerosis patients or remove excess mucus in cystic fibrosis patients.
Crucially, these multicellular organisms have a finite lifespan, naturally degrading after four to six weeks. This “kill switch” prevents potentially invasive cell growth.
Understanding how some cells continue functioning and metamorphosing into multicellular entities post-mortem could revolutionise personalised and preventive medicine. The discovery of this third state not only redefines our understanding of life and death but also opens up exciting possibilities for future medical treatments.
