The Cells That Exist Between Life and Death

After death, some cells can enter what's known as 'the third state' to create new life

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As much as our species has learned about ourselves, our world, and Life itself, some major mysteries remain. Perhaps no mystery is greater than death — not Space, the bottom of our oceans, or even the human mind. Everything alive will die; it is a fact. Yet we have little to no idea what, if anything, happens after death.

Still, we know enough to know that death and life are a cycle. Everything alive will die, but with death comes life. While any potential spiritual journey or afterlife remains unknown, scientists are studying the physical aspects of the cycle — and they’ve identified cells that exist somewhere between both.

The Curiosity

Our story begins with biologist Peter Nobel from the University of Washington and bioinformatics researcher Alex Pozhitkov from the City of Hope’s cancer center in California, who describe themselves as “researchers who investigate what happens within organisms after they die.”

While life and death’s cycle makes for great poetry, scientists typically consider death to be when an organism irreversibly ceases to function as a whole. In the grand scheme of things, death is indeed irreversible, but Pozhitkov and Nobel found it may be transformable.

For instance, organ donation demonstrates how organs, cells, and tissues can survive after the original organism dies. Considering this, Nobel and Pozhitkov wondered:

What mechanisms allow certain cells to keep working after an organism has died?

So, the duo followed their curiosity and gathered as many studies as possible from the last few years in search of an answer. Their findings led to a comprehensive analysis published in July 2024 by the journal Physiology.

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The Third State

Put simply, the researchers identified some cells that exist in a “third state,” which challenges our understanding of cell behavior.

In an article about their research, Nobel and Pozhitkov wrote in The Conversation that while there are some examples of developmental transformations in nature — such as caterpillars turning into butterflies or tadpoles becoming frogs — there are few examples of organisms changing in “ways that are not predetermined.”

They point out that while organoids, tumors, and cell lines can divide indefinitely in a petri dish, they don’t develop new functions.

Meanwhile, Nobel and Pozhitkov’s analysis reveals cells that change in non-predetermined ways and develop new functions after their transformation.

Xenobots and Anthrobots

In their Conversation article, the researchers focus on a pretty awesome study from 2021 by researchers at Tufts and Harvard Universities in Massachusetts, the University of Vermont, and the New Jersey Institute of Technology.

The researchers extracted skin cells from deceased frog embryos and discovered the cells adapted to their new petri dish conditions in the team’s lab by reorganizing themselves into multicellular organisms. Astonishingly, the organisms began behaving in new ways that differed from their original biological roles.

For instance, before their transformation, when the frog cells were still part of a living frog embryo, they used cilia – small, hair-like structures – to move mucus. However, after the frog died and the cells reorganized, they used their cilia to travel and navigate their surroundings. The scientists named these new lifeforms xenobots.

Douglas Blackiston, a senior scientist at Tufts University who led the 2021 study, explained to Charlotte Hu of Popular Science:

“At the most basic level, this is a platform or way to build with cells and tissues, the way we can build robots out of mechanical components. You can almost think of it as Legos, where you can combine different Legos together, and with the same set of blocks you can make a bunch of different things.”

In The Conversation, Nobel and Pozhitkov say that beyond xenobots’ unique ability to transform after their hosts’ death, these newly formed organisms can perform kinematic self-replication. In other words, they can physically replicate their function and structure without growing. This trait is particularly incredible since most cells that replicate grow on or within the host organism’s body.

A couple of years later, in 2023, researchers discovered that some individual human lung cells can also reorganize into a new, self-propelling organism. Named anthrobots, these organisms are capable of even more than xenobots because, beyond navigating their surroundings, they can also heal themselves and injured neuron cells.

In their article, Nobel and Pozhitkov write:

“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.”

Now that scientists know the third state exists, the next step is to understand how this transformation happens and how many cell types are capable of it.

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How it Happens

Scientists have already identified many factors influencing whether cells or tissues can not just survive but function after their host organism dies. Things like metabolic activity, environmental conditions, trauma, infection, and the time elapsed since death significantly affect tissue and cell viability.

After all, different cell types have different lifespans. For instance, human white blood cells die between about two to four days after a person’s death. Meanwhile, skeletal muscle cells in mice can keep growing for as long as two weeks after the mice die, and sheep and goat fibroblast cells can be cultured for up to a month postmortem.

Yet, none of these factors explain why this transformation happens at all. Though, of course, scientists thought of some possibilities. In their analysis, Nobel and Pozhitkov wrote:

“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 execute specific functions such as growth and movement, shaping the structure of the organism they form.”

Further, previous research suggests there’s likely a diverse range of cell types beyond xenobots and anthrobots capable of transformation postmortem. Already, certain genes related to immunity, stress, and epigenetic regulation in humans, zebrafish, and mice have been identified as becoming active after death. So, the next step is to figure out just how widespread this transformative ability postmortem is, and how we can use the third state to benefit humans.

In the Future

The third state of cell transformation is exciting because it gives scientists more insight into cell adaptability. However, the discovery's more immediate value is in its medical potential for preventive and personalized treatments.

For instance, in the future, it may be possible that cells farmed from a patient’s living tissue could then be engineered into anthrobots to deliver medications to the patient without triggering an undesirable immune response. Nobel and Pozhitkov explain in The Conversation:

“Engineered anthrobots injected into the body could potentially dissolve arterial plaque in atherosclerosis patients and remove excess mucus in cystic fibrosis patients.”

Crucial to this idea is that these multicellular organisms don’t live forever. They naturally degrade after about four to six weeks in a process known as the “kill switch,” which prohibits the infinite growth or transformation of potentially invasive cells.

There is still much to learn about this biological third state of cell existence, but what scientists learned so far clearly shows plenty of promising potential.

Perspective Shift

The idea that doctors in the future could create anthrobots harvested cells from our own tissues to deliver medication seems like something straight out of a science-fiction novel, yet it’s a very science-nonfiction reality.

And in an abstract but very real way, the mere existence of anthrobots and xenobots demonstrates that our long-held human observation that life and death are not a binary but a cycle is right.

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Image Source: WikiCommons - The xenobot shown “is layered with heart muscle (now glowing red). AI determines the overall shape of the organism, as well as the location of its muscle, to produce forward movement.”