Life and death are traditionally viewed as opposites. But the emergence of new multicellular life-forms from the cells of a dead organism introduces a “third state” that lies beyond the traditional boundaries of life and death.
Usually, scientists consider death to be the irreversible halt of functioning of an organism as a whole. However, practices such as organ donation highlight how organs, tissues and cells can continue to function even after an organism’s demise. This resilience raises the question: What mechanisms allow certain cells to keep working after an organism has died?
We are researchers who investigate what happens within organisms after they die. In our recently published review, we describe how certain cells – when provided with nutrients, oxygen, bioelectricity or biochemical cues – have the capacity to transform into multicellular organisms with new functions after death.
Life, death and emergence of something new
The third state challenges how scientists typically understand cell behavior. While caterpillars metamorphosing into butterflies, or tadpoles evolving into frogs, may be familiar developmental transformations, there are few instances where organisms change in ways that are not predetermined. Tumors, organoids and cell lines that can indefinitely divide in a petri dish, like HeLa cells, are not considered part of the third state because they do not develop new functions.
However, researchers found that skin cells extracted from deceased frog embryos were able to adapt to the new conditions of a petri dish in a lab, spontaneously reorganizing into multicellular organisms called xenobots. These organisms exhibited behaviors that extend far beyond their original biological roles. Specifically, these xenobots use their cilia – small, hair-like structures – to navigate and move through their surroundings, whereas in a living frog embryo, cilia are typically used to move mucus.
Xenobots are also able to perform kinematic self-replication, meaning they can physically replicate their structure and function without growing. This differs from more common replication processes that involve growth within or on the organism’s body.
Researchers have also found that solitary human lung cells can self-assemble into miniature multicellular organisms that can move around. These anthrobots behave and are structured in new ways. They are not only able to navigate their surroundings but also repair both themselves and injured neuron cells placed nearby.
Taken together, these findings demonstrate the inherent plasticity of cellular systems and challenge the idea that cells and organisms can evolve only in predetermined ways. The third state suggests that organismal death may play a significant role in how life transforms over time.