I got a bit of a jolt from this September 12, 2024 essay by Peter A Noble, affiliate professor of microbiology at the University of Washington, and Alex Pozhitkov, senior technical lead of bioinformatics, Irell & Manella Graduate School of Biological Sciences at City of Hope, for The Conversation (h/t Sept. 12, 2024 item on phys.org), Note: Links have been removed,

Life and death are traditionally viewed 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.

Usually, scientists consider death to be the irreversible halt of 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 demise. This resilience raises the question: What mechanisms allow certain cells to keep working after an organism has died?

We are researchers who investigate what happens within organisms after they die. In our recently published review, we describe how certain cells – when provided with nutrients, oxygen, bioelectricity or biochemical cues – have the capacity to transform into multicellular organisms with new functions after death.

Life, death and emergence of something new

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 [cervical cancer cells taken from Henrietta Lacks without her knowledge], are not considered part of the third state because they do not develop new functions.

However, researchers found that skin cells extracted from deceased frog embryos were able to adapt to the new conditions of a petri dish in a lab, spontaneously reorganizing into multicellular organisms called xenobots [emphasis mine]. These organisms exhibited behaviors that extend far beyond their original biological roles. Specifically, these xenobots use their cilia – small, hair-like structures – to navigate and move through their surroundings, whereas in a living frog embryo, cilia are typically used to move mucus.

Xenobots are also able to perform kinematic self-replication, meaning 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 found that solitary human lung cells can self-assemble into miniature multicellular organisms that can move around. These anthrobots [emphasis mine] behave and are structured in new ways. They are not only able to navigate their surroundings but also repair both themselves and injured neuron cells placed nearby.

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.

…

I had not realized that xenobots are derived from dead frog embryos something I missed when mentioning or featuring them in previous stories, the latest in a September 13, 2024 posting, which also mentions anthrobots. Previous stories were published in a June 21, 2021 posting about xenobots 2.0 and their ability to move and a June 8, 2022 posting about their ability to reproduce. Thank you to the authors for relieving me of some of my ignorance.

For some reason I was expecting mention, brief or otherwise, of ethical or social implications but the authors offered this instead, from their September 12, 2024 essay, Note: Links have been removed,

Implications for biology and medicine

The third state not only offers new insights into the adaptability of cells. It also offers prospects for new treatments.

For example, anthrobots could be sourced 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 life span, 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 some time after an organism’s demise holds promise for advancing personalized and preventive medicine.

I look forward to hearing about the third state and about any ethical or social issues that may arise from it.