Life and death are traditionally seen 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.
Traditionally, scientists view death as the irreversible cessation of the 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 the death of an organism. This resilience raises the question: What mechanisms allow certain cells to continue to function after an organism has died?
We are researchers who investigate what happens in organisms after they die. In our recently published review we describe how certain cells - when supplied with nutrients, oxygen, bioelectricity or biochemical signals - have the capacity to transform into multicellular organisms with new functions after death.
Life, Death and the Rise of Something New
The third state challenges how scientists typically understand cell behavior. While caterpillars turning into butterflies or tadpoles evolving into frogs may be familiar developmental transformations, there are few cases in which organisms change in ways that are not predetermined. Tumors, organoids, and cell lines that can divide indefinitely in a petri dish, such as HeLa cells, are not considered to be in the third state because they do not develop new functions.
However, researchers found that skin cells taken from dead frog embryos could adapt to the new conditions in a lab petri dish and spontaneously reorganize into multicellular organisms called xenobots. These organisms exhibited behaviors that went far beyond their original biological roles. These xenobots use their cilia-tiny, hair-like structures-to navigate and move through their environment, while cilia in a living frog embryo are typically used to move mucus.
Xenobots can also perform kinematic self-replication, meaning that 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 discovered that solitary human lung cells can self-assemble into miniature multicellular organisms that can move around. These anthropologists behave and are structured in new ways. They are able not only to navigate their environment, but also to repair themselves and injured neuron cells that are placed nearby.
Taken together, these findings demonstrate the inherent plasticity of cellular systems and challenge the idea that cells and organisms can only evolve in predetermined ways. The third state suggests that the death of organisms may play an important role in how life transforms over time.
Post-mortem conditions
Several factors influence whether certain cells and tissues can survive and function after an organism dies. These include environmental conditions, metabolic activity, and preservation techniques.
Different cell types have different survival times. For example, in humans, white blood cells die between 60 and 86 hours after the death of the organism. In mice, skeletal muscle cells can regrow after 14 days postmortem, while sheep and goat fibroblast cells can be cultured for up to about a month postmortem.
Metabolic activity plays a major role in whether cells can continue to survive and function. Active cells that require a continuous and substantial energy supply to maintain their function are more difficult to culture than cells with lower energy requirements. Preservation techniques such as cryopreservation can ensure that tissue samples such as bone marrow function in the same way as those from living donor sources.
Inherent survival mechanisms also play an important role in whether cells and tissues continue to live. 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, probably to compensate for the loss of homeostasis. In addition, factors such as trauma, infection, and the time elapsed since death have a significant impact on tissue and cell viability.
Factors such as age, health, sex, and species further shape the postmortem landscape. This is reflected in the challenge of culturing and transplanting metabolically active islet cells, which produce insulin in the pancreas, from donors to recipients. Researchers believe that autoimmune processes, high energy costs, and the breakdown of protective mechanisms may be the reason behind many failed islet transplants.
How these variables interact to allow certain cells to continue functioning after an organism dies remains unclear. One hypothesis is that specialized channels and pumps embedded in the outer membranes of cells serve as intricate electrical circuits. These channels and pumps generate electrical signals that allow cells to communicate with each other and perform specific functions, such as growth and movement, thereby shaping the structure of the organism they form.
The extent to which different cell types can transform after death is also uncertain. Previous research has shown that specific genes involved in stress, immunity, and epigenetic regulation are activated after death in mice, zebrafish, and humans, suggesting widespread potential for transformation among diverse cell types.
Implications for biology and medicine
The third state not only offers new insights into the adaptability of cells. It also offers perspectives for new treatments.
For example, anthrobots could be extracted from an individual's living tissue to deliver drugs without triggering an unwanted immune response. Engineered anthrobots injected into the body could potentially dissolve arterial plaque in atherosclerosis patients and remove excess mucus in cystic fibrosis patients.
Importantly, these multicellular organisms have a finite lifespan and naturally degrade after four to six weeks. This "kill switch" prevents the growth of potentially invasive cells.
A better understanding of how some cells continue to function and metamorphose into multicellular entities some time after an organism has died offers prospects for the development of personalized and preventive medicine.
Article updated to reflect Peter Noble's current academic affiliation. This article is republished from The Conversation, a nonprofit, independent news organization that brings you facts and reliable analysis to help you understand our complex world. It was written by: Peter A Noble, University of Alabama at Birmingham and Alex Pozhitkov, Irell & Manella Graduate School of Biological Sciences at City of Hope Read more: The authors are not employees of, consultants to, own shares in, or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.
