When we think of death, we imagine a final, irreversible end. But what if death is not as absolute as it seems? What if some parts of us — our cells, our tissues — continue to fight for survival, even after our hearts have stopped beating? Enter the morbid yet fascinating world of postmortem biology.
Researchers have found that some cells form new multicellular structures with functions that defy their original biological roles even long after the organism they once belonged to has died. They call this the “third state” — a phenomenon that walks the fine line between life and death.
The findings are riveting and could have profound implications for medicine, from organ transplantation to regenerative therapies.
The Third State: Life Beyond Death
Researchers led by Peter Noble, Associate Professor of Microbiology at the University of Alabama at Birmingham, conducted a review of multiple previously published studies on post-mortem biology. They conclude that under the right conditions, cells from deceased organisms can reorganize into entirely new multicellular entities. These entities, known as xenobots and anthrobots, exhibit behaviors far beyond their original biological roles.
Take xenobots, for example. These tiny, self-assembling organisms are created from skin cells extracted from dead frog embryos. In a petri dish, these cells spontaneously reorganize into multicellular structures that can move, heal, and interact with their environment. Unlike the cilia in living frog embryos, which typically move mucus, the cilia in xenobots enable them to navigate their surroundings. Even more astonishing, xenobots can replicate their structure and function without growing — a process known as kinematic self-replication.
Similarly, human lung cells have been observed self-assembling into anthrobots, miniature multicellular organisms capable of moving and repairing damaged neuron cells.
This sort of plasticity raises the possibility that maybe in the future, we might be able to harness it to repair damaged tissues or even grow new organs.
“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,” the researchers wrote in a blog post for The Conversation.
Some Cells are “Unaware”
The main objective of this study was to explore how cells and tissues respond to the death of the organism they once belonged to. “In life, genetic and epigenetic networks precisely coordinate the expression of genes,” the authors write. “However, most networks fail in organismal death, yet some continue to function despite the loss of the ‘whole.’”
They found that the way a person dies — whether quickly from trauma or slowly from a prolonged illness — affects how their cells respond. In cases of slow death, certain genes associated with survival and development were activated. “The skin of humans who have already undergone slow death shows induction of developmental pathway genes,” the study notes. These genes work with pathways that regulate cell growth, repair, and even embryonic development.
Remarkably, some cells seemed almost unaware that the host had died. Fibroblasts, a type of cell found in connective tissue, continued to communicate with each other, as if carrying on with their normal functions. “The fibroblasts are almost ‘unaware’ that the host is gone,” the researchers observed. “They continue to operate and communicate.”
The temporary yet relatively long survival of these cells after an organism’s death hinges several factors. These include environmental conditions, metabolic activity, and even preservation techniques. For instance, white blood cells in humans can survive for up to 86 hours postmortem. Meanwhile skeletal muscle cells in mice have been regrown as late as 14 days after death. Cryopreservation techniques can extend the viability of tissues like bone marrow, allowing them to function similarly to living donor sources.
Cells with high energy demands, such as pancreatic islet cells, are harder to keep alive after death. In contrast, cells with lower energy requirements, like fibroblasts from sheep and goats, can be cultured for weeks postmortem. Researchers have also observed a surge in the activity of stress-related and immune-related genes after death. This is likely a response to the loss of homeostasis.
The Third State in Medicine
These resilient cells could make their way into new therapies and exciting biotech applications. Anthrobots, for example, could be engineered from a patient’s own tissue to deliver drugs without triggering an immune response. They might dissolve arterial plaque in atherosclerosis patients or clear excess mucus in those with cystic fibrosis. And because these multicellular organisms naturally degrade after four to six weeks, they come with a built-in “kill switch” that prevents them from becoming invasive.
Understanding how cells survive after death could also be a game-changer for organ transplantation. Currently, the window for harvesting viable organs is narrow. Hearts and lungs must be transplanted within approximately four hours of being removed from the donor. But this study suggests that with the right interventions, that window could be widened.
One of the most intriguing questions raised by the study is whether consciousness persists after death. While the brain is highly sensitive to oxygen deprivation, some brain cells can survive for hours without oxygen. The researchers cite studies showing that bursts of brain activity can occur up to 80 minutes after cardiac arrest.
“If hypoxic brain cells are still alive, do organisms retain consciousness?” the authors ask. A study of cardiac arrest patients found that some reported vivid memories and sensations during the time they were clinically dead.
These experiences included feelings of separation from the body, a sense of moving toward a destination, and a re-evaluation of life — what people commonly refer to as “near-death experiences”. While the scientific community remains divided on the nature of these experiences, the findings suggest that the traditional criteria for determining death may need to be reevaluated.
