Life and death have traditionally been viewed as opposites. However, the emergence of new multicellular life forms from the cells of a dead organism introduces a “third state” beyond the traditional boundaries of life and death. Scientists typically view death as the irreversible cessation of the body’s ability to function as a whole. However, practices such as organ donation highlight how organs, tissues, and cells can continue to function even after an organism has died.

This insistence raises the question: What mechanisms allow certain cells to continue functioning after an organism’s death?

We are researchers who study what happens to organisms after they die. In our recently published review, we explain how certain cells, when supplied with nutrients, oxygen, bioelectrical or biochemical signals, have the ability to develop into multicellular organisms with new functions after death.

Life, death and the emergence of something new

The third situation challenges the way scientists usually understand cells to behave. While caterpillars turning into butterflies or tadpoles turning into frogs are familiar developmental transformations, there are a few examples of organisms changing in unexpected ways.

Tumors, organoids, and cell lines that can divide indefinitely in a petri dish, such as HeLa cells, are not considered part of the third case because they do not develop new functions. But the researchers found that skin cells from dead frog embryos could adapt to the new conditions of the lab Petri dish and spontaneously reorganize into multicellular organisms called xenobots.

These organisms exhibited behaviors far beyond their original biological roles. Specifically, these xenobots use cilia (tiny, hair-like structures) to navigate and move, whereas in living frog embryos, cilia are normally used to move mucus.

Xenobots are also capable of kinematically self-reproducing, meaning that they can physically reproduce their structures and functions without growth. This is different from more common replication processes that involve growth within or on an organism’s body.

Researchers have also discovered that individual human lung cells can self-assemble into miniature multicellular organisms capable of locomotion. These antrobots behave and are structured in a novel way. They can not only navigate their environment, but also repair themselves and nearby damaged neuron cells.

Taken together, these discoveries reveal the inherent plasticity of cellular systems and challenge the idea that cells and organisms can only develop in predetermined ways. The third aspect suggests that the death of an organism may play a significant role in how life evolves over time.

Post-mortem conditions

A variety of factors affect whether particular cells and tissues can survive and function after an organism dies. These include environmental conditions, metabolic activity, and preservation methods. Different cell types have different survival times. For example, in humans, leukocytes die 60 to 86 hours after the organism dies. Skeletal muscle cells in mice can regrow 14 days after death, while fibroblast cells from sheep and goats can be cultured for about a month after death.

Metabolic activity plays a major role in whether cells can survive and function. Active cells, which require a constant and significant amount of energy to maintain their function, are more difficult to culture than cells with lower energy requirements. Preservation techniques such as cryopreservation may allow tissue samples, such as bone marrow, to function as well as living donor sources.

Intrinsic survival mechanisms also play an important role in whether cells and tissues survive. For example, researchers have observed a significant increase in the activity of stress-related genes and immune-related genes after the death of the organism, which probably compensates for the loss of homeostasis. Factors such as trauma, infection, and time since death also significantly affect the viability of tissues and cells.

Factors such as age, health, sex, and species further shape the postmortem landscape. This is seen in the difficulty of culturing and transplanting metabolically active insulin-producing islet cells from the pancreas from donors to recipients. Researchers believe that autoimmune processes, high energy costs, and impaired defense mechanisms may be responsible for many islet transplant failures.

How the interaction of these variables allows certain cells to continue to function after the organism’s death remains unclear. One hypothesis is that specialized channels and pumps embedded in the cells’ outer membranes serve as complex electrical circuits.

These channels and pumps produce electrical signals that allow cells to communicate with each other, perform specific functions such as growth and movement, and shape the structure of the organism they form.

The extent to which different cell types can undergo transformation after death is also unknown. Previous studies have shown that specific genes involved in stress, immunity, and epigenetic regulation are activated after death in mice, zebrafish, and humans, suggesting a broad potential for transformation across different cell types.

Importance for biology and medicine

The third situation not only offers a new perspective on the adaptability of cells, but also opens up hopes for new treatments.

For example, anthrobots could be derived from living human tissue to deliver drugs without triggering an unwanted immune response. Engineered anthrobots injected into the body could potentially dissolve arterial plaque in patients with atherosclerosis and remove excess mucus in patients with cystic fibrosis.

Importantly, these multicellular organisms have a limited lifespan and naturally degrade after four to six weeks. This “switch” prevents the growth of potentially invasive cells.

A better understanding of how some cells continue to function and develop into multicellular entities after the death of the organism holds promise for the development of personalized and preventive medicine.