Life and death are traditionally seen as opposites. But the emergence of new multicellular life forms from the cells of a dead organism ushers in a “third state” that extends beyond the traditional boundaries of life and death.
Usually, scientists consider 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 an organism’s death.
This resilience raises the question: What mechanisms allow certain cells to continue working after an organism has died?
We are researchers who investigate what happens inside organisms after they die. In our recently published review, we describe how some cells—when provided with nutrients, oxygen, bioelectricity, or biochemical signals—have the ability to transform into multicellular organisms with new functions after death.
Life, death and the emergence of something new
The third condition challenges the way scientists typically understand cell behavior. While caterpillars metamorphosing into butterflies, or chickens evolving into frogs, may be well-known developmental transformations, there are few cases where 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 part of the third state because they do not develop new functions.
However, the researchers found that skin cells extracted from dead frog embryos were able to adapt to the new conditions of a petri dish in a laboratory, spontaneously reorganizing into multicellular organisms called xenobots.
These organisms exhibited behaviors that extended far beyond their original biological roles. Specifically, these xenobots use their cilia—tiny, hair-like structures—to navigate and move through their environment, whereas in a living frog embryo, cilia are typically used to move mucus.
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Xenobots are also capable of kinematic self-replication, meaning they can physically replicate their structure and function without growing. This differs from the more common processes of reproduction that involve growth within or on the organism’s body.
Researchers have also discovered that single human lung cells can self-assemble into miniature multicellular organisms that can move around. These anthropots behave and structure in new ways. They are not only able to navigate their surroundings, but also repair themselves and nearby damaged neuron cells.
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 condition suggests that the death of the organism may play an important role in how life transforms over time.
Conditions after death
Several factors affect whether certain cells and tissues can survive and function after an organism dies. These include environmental conditions, metabolic activity and storage techniques.
Different types of cells 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 be reproduced after 14 days after death, while fibroblast cells from sheep and goats can be cultured up to a month or more after death.
Metabolic activity plays an important role if cells can continue to survive and function. Active cells that require a constant and substantial supply of energy to maintain their function are more difficult to culture than cells with lower energy requirements.
Preservation techniques such as cryopreservation can allow tissue samples such as bone marrow to function similarly to living donor sources.
Innate survival mechanisms also play a key role in whether cells and tissues 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, which likely compensates for the loss of homeostasis.
Additionally, factors such as trauma, infection, and time since death significantly affect tissue and cell viability.
Factors such as age, health, sex, and species type further shape the landscape after death. This is seen in the challenge of cultivating 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 degradation of defense mechanisms may be the reason for many islet transplant failures.
It remains unclear how the interplay of these variables allows certain cells to continue to function after an organism dies. 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, shaping the structure of the organism they form.
The extent to which different cell types can undergo postmortem transformation is also uncertain. Previous research has found 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 between different cell types.
Implications for biology and medicine
The third state not only provides new insights into cell adaptability. It also offers prospects for new treatments.
For example, anthrobots can be taken from an individual’s living tissue to deliver drugs without triggering an unwanted immune response. Engineered anthrobots injected into the body can dissolve arterial plaque in patients with atherosclerosis and remove excess mucus in patients with cystic fibrosis.
Importantly, these multicellular organisms have a limited lifespan, naturally degrading 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 long after an organism’s death holds promise for advancing personalized and preventive medicine.
Peter A Noble, Professor of Microbiology, University of Washington and Alex Pozhitkov, Senior Technical Director of Bioinformatics, Irell & Manella Graduate School of Biological Sciences in the City of Hope
This article is republished from The Conversation under a Creative Commons license. Read the original article.