Sentient cells as basic units of tissues, organs and organismal physiology

Cells evolved some 4 billion years ago, and since then the integrity of the structural and functional continuity of cellular life has been maintained via highly conserved and ancient processes of cell reproduction and division. The plasma membrane as well as all the cytoplasmic structures are reproduced and inherited uninterruptedly by each of the two daughter cells resulting from every cell division. Although our understanding of the evolutionary emergence of the very first cells is obscured by the extremely long timeline since that revolutionary event, the generally accepted position is that the de novo formation of cells is not possible; all present cells are products of other prior cells. This essential biological principle was first discovered by Robert Remak and then effectively coined as Omnis Cellula e Cellula (every cell of the cell) by Rudolf Virchow: all currently living cells have direct structural and functional connections to the very first cells. Based on our previous theoretical analysis, all cells are endowed with individual sentient cognition that guides their individual agency, behaviour and evolution. There is a vital consequence of this new sentient and cognitive view of cells: when cells assemble as functional tissue ecologies and organs within multicellular organisms, including plants, animals and humans, these cellular aggregates display derivative versions of aggregate tissue‐ and organ‐specific sentience and consciousness. This innovative view of the evolution and physiology of all currently living organisms supports a singular principle: all organismal physiology is based on cellular physiology that extends from unicellular roots.

dramatically changed after the emergence of photosynthetic archaea and cyanobacteria some 3.6 billion years ago (Fournier et al., 2021).Intriguingly, life was exclusively based on these relatively simple archaeal and bacterial cells for about 2 billion years until the first eukaryotic cells emerged some 2.4-1.7 billion years ago (Bengtson, Sallstedt et al., 2017;Bengtson, Rasmussen, et al., 2017;Porter, 2020).Instead of viewing the first 2 billion years as a fallow time in evolution, it should be viewed as an active period during which ancient cells first assembled and integrated their metabolic and physiological processes, evolving alongside and under the tight control of a cellular sentience apparatus as its cellular senome.The cellular senome is proposed to orchestrate all cellular metabolic activities and is best thought of as the complete sensory apparatus of the cell, forming the basis of its sensory experiences (Baluška & Miller, 2018).Accordingly, just as the genome represents a summation of the heritable, reproductive genomic endowment of a cell, and the epigenome is the sum total of the environmentally induced chemico-physical modifications of that genetic endowment, the senome is the effective apparatus that links the cellular reception of external environmental cues to its productive cellular deployment (Baluška & Miller, 2018;Miller et al., 2020aMiller et al., , 2020b).As we discuss below for the complex eukaryotic cell, the larger host cell is proposed to have its sentience supported by the actin cytoskeleton, whereas the smaller guest cell relied on the tubulin/centrin cytoskeleton-based sentience.
Besides the cytoskeleton, the cellular sentience-generating apparatus is based on the excitable plasma membrane populated by numerous sensors, receptors, channels and diverse transporters, working together as biological versions of Maxwell demons (Boël et al., 2019;Mizraji, 2021;Flatt et al., 2023).Together, these cellular architectural elements constitute the bulwark of cellular senomic awareness.In our Cellular Basis of Consciousness (CBC) theory (Reber, 2019;Reber et al. 2023), we proposed that the plasma membrane not only protects cells from the challenging environment but also allows the generation of the senome-based charged molecules, including diverse ions, and reactive radical species including charged molecules such as lipids, sugars, peptides, proteins and cytoskeletal polyelectrolyte-like biopolymers which all contribute to individual cellular subjective experiences (Baluška & Miller, 2018;Baluška & Mancuso, 2019;Tuszynski, 2019;Cruz et al., 2021;Alva et al., 2022;Hunley & Marucho, 2022).Sensory events at the plasma membrane modify the architectures of diverse intracellular senomic fields via the ordered release and annihilation of charged biomolecules.Every single charged senomic biomolecule acts on all others in complex and ordered patterns that have evolved over billions of years of cellular evolution.
The senomic apparatus is proposed to act as bioelectromagnetic fields permeating cells and energizing an electrolyte-based bioplasm animating all cellular biomolecules (Baluška & Miller, 2018).In other words, the cellular senome supports cellular sentience as the embodied mind of the cell.In this manner, the senome supplements the genome and epigenome as a third informational medium that stores sensory information as effective cellular memory to enable learning, thereby constituting the epicentre of cellular experientiality (Baluška & Miller, 2018;Miller et al., 2019Miller et al., , 2020aMiller et al., , 2020b;;Reber et al. 2023).The electromagnetic nature of cellular senomic fields suggests that they radiate beyond cellular boundaries.In this way, the cell can directly and effectively sense its environment, including the senomic fields of adjacent cells, animating cells to rapidly adjust to actual external environmental situations.Importantly, the senome can modify arrangements of its components within seconds or even less, reflecting the changing parameters of the surrounding cellular environment, thereby allowing for the very tight coupling of the cell with its current biotic and abiotic environment.
Thus, the senome delivers contemporaneous environmental information to cells about their outside space, triggering capable internally generated models of external space and enabling predictions about future conditions, permitting their rapid adaptation and survival.In other words, the senome acts akin to a replete sensory and sentience organ supporting cellular cognition, behaviour and adaptation.The various behavioural consequences of these biomolecular processes can be seen in the range of cognitive functions displayed by cells, including learning, navigational skills, memory formation, decision-making and communication.See Reber (2019) and Baluška et al. (2022Baluška et al. ( , 2023aBaluška et al. ( , 2023b) ) for details on these functions.
Naturally, then, the senome forms the foundation of cell-cell communication, which ultimately culminated in the endosymbiotic generation of complex eukaryotic cells out of several originally independent prokaryotic cells (Baluška et al., 2004a(Baluška et al., , 2004b)).Therefore, senome-based cellular sentience is crucial for the organismal sense of 'self' constituting the basis of competent cognitive closure embodied within all unicellular organisms.All multicellular consciousness is its derivative (Miller, 2016;Reber, 2019;Reber et al., 2023).In our CBC concept, subjectivity is defined by the cell membrane enclosing the inside space (subjective self) from the outside (objective environment).The mystery remains how two cells could integrate together to assemble the supracellular ʻselfʼ.
Cell sentience is inherently linked to circadian redox clocks of cells.The formation of the first true cells from hypothetical proto-cells was accomplished on an ancient Earth that was already spinning around its own axis with a 24 h periodicity.In that case, primordial cellular circadian clocks would have presumably assembled together and integrated with hypothetical ancient senomic fields.Precise predictions of environmental changes via cognitive cellular clocks integrated with cell sentience were essential for cellular survival in ancient times as well as today (Baluška & Reber, 2021).In support of this scenario, well-known genomic clocks were discovered to be preceded by and integrated with more ancient redox clocks based on peroxiredoxins (Edgar et al., 2012;Stangherlin & Reddy, 2013;Reddy & Rey, 2014;Hoyle & O'Neill, 2015;del Olmo et al., 2019).Importantly, these redox cycles are conserved in both prokaryotic and eukaryotic cells, operating in semi-independent modes even in symbiotic organelles of eukaryotic cells (Dietz et al., 2006;Cox et al., 2009).We can presume that these circadian redox clocks descended from the most ancient redox clocks of the first cells (Baluška & Reber, 2021) evolving some 3-4 billion years ago.

The eukaryotic cell is a multicellular system assembled by sentient prokaryotic cells
It took some 2 billion years of prokaryotic life for the emergence of the first eukaryotic cells.The emergence of eukaryotic cells represents the most radical transition in cellular evolution.It remains a mystery how and why ancient prokaryotic cells assembled the first eukaryotic cell.Several scenarios are possible, including predatory, parasitic or symbiotic ones.One advance in our understanding of this mystery has been the discovery that Asgard archaea show several eukaryotic features, especially an actin cytoskeleton supporting filopodia-like cellular protrusions associated with vesicle trafficking systems (Stairs & Ettema, 2020;Rodrigues-Oliveira et al., 2023).Moreover, the discovery of archaeal fusexins (Moi et al., 2022), which are known to drive cell-cell fusion of eukaryotic sex cells (gametes) allowing their sexual reproduction (Brukman et al., 2022;Lu & Ikawa, 2022), adds further support for eukaryotes as a combination of an archaeal actin-based host cell and a tubulin/centrin-based guest cell (Baluška et al., 2004a(Baluška et al., , 2004b;;Baluška & Lyons, 2018, 2021).
Intriguingly, there are close similarities between these two hypothetical cells and today's large, non-motile actin-based oocytes and small, tubulin/centrin-based sperm cells (Baluška et al., 2023a(Baluška et al., , 2023b)).Nonetheless, how two independent organisms negotiated their further life as unitary organisms and effectively melded one self-identity out of two previous, independent ones remains an enigma.Our proposal is that the senome concept offers a basis of resolution of how two or more cells can unite into one sentient 'self' .To do so, they F. Baluška and others J Physiol 602.11 must share a common information space so there can be concordant evaluation of environmental cues in the new entity that permits coordinated action among the previously separate parts.The vehicle for that shared appraisal of environmental information is the N-space episenome, assembled from contributions from their previously separate senomes, as discussed in earlier papers (Miller et al., 2020a(Miller et al., , 2020b) ) and the book The Sentient Cell.The Cellular Foundations of Consciousness (Reber et al., 2023).
In the next section, we will discuss the organismal nature of both prokaryotic and eukaryotic organisms, either as single prokaryotic cells or eukaryotic cells that combine to effect multicellularity.Notably, in the CBC theory, the long evolutionary time that passed from ancient prokaryotes until the fully competent eukaryotic cell entered the evolutionary scene is expressly due to difficulties merging two independent senomes together into one fully integrated supracellular senomic field.We propose that only when this new, unitary supracellular senome was generated could the necessary cognitive closure be attained for a unitary self at a higher level of biological complexity.We further argue that this feature helps explain why it is not accidental that all eukaryotic multicellular organisms are symbiotic holobionts (Miller, 2016).The perpetual continuation of cells from the first prokaryotes forward is based on the continuous lineage of the plasma membrane as the foundation of a cellular senome, thus permitting cross-communication among the senomic fields of both prokaryotes and eukaryotes.Consequently, holobionts are an expression of the maintenance of a perpetual senomic kinship that has underscored 4 billion years of cellular life.

Unicellular organisms -every cell as an independent and autonomous organism
Although prokaryotic archaea and bacteria appeared very early after the formation of Earth, they continue to exist as independent unicellular organisms.As discussed above, some of these prokaryotic cells merged together to generate the supracellular assembly known as the eukaryotic cell some 2.4-1.7 billion years ago (Bengtson, Sallstedt et al., 2017;Bengtson, Rasmussen, et al., 2017;Porter, 2020).Their redox-based circadian clocks obviously pre-date the genomic circadian clocks and are based on oxidation-reduction cycles of peroxiredoxins (Edgar et al., 2012;Reddy & Rey, 2014;Hoyle & O'Neill, 2015).Peroxiredoxins represent an abundant class of thiol peroxidases that presumably act as redox sensors and control cellular redox homeostasis within both eukaryotic cells and their symbiotic organelles (Dietz et al., 2006;Cox et al., 2009).Prokaryotic organisms are the most successful planetary life systems and most of them would survive even if all multicellular life were terminated due to some planetary catastrophe.Their 4 billion year history of uninterrupted life makes them extraordinarily robust and resilient.Nevertheless, they communicate abundantly and competently resist viruses using their prokaryotic version of immunity (Koonin & Makarova, 2013;Barrangou & Marraffini, 2014).This prokaryotic immunity not only allows prokaryotic organisms to fight their parasites but also to communicate this resistance to other organisms and to pass it on to their progeny (Marraffini, 2015).These communicative aspects of prokaryotic life are the most crucial issues in their survival and figure significantly in the evolution of eukaryotic cells and multicellular organisms.
The central theme of the evolution and development of multicellular organisms is cell-cell communication at multiple levels (Arias, 2023).Indeed, infection dynamics, especially viral infections, should be considered another form of cross-communication among the cellular domains and the virome (Baluška, 2009;Witzany, 2010;Witzany & Baluška, 2014;Villarreal & Witzany, 2019, 2023;Miller et al., 2023).We will discuss this forgotten aspect of cell biology and suggest that this feature is essential for our understanding of all multicellular organisms, including humans.

Multicellular organisms -every cell as a semi-autonomous organism
Ever since the earliest version of Cell Theory was formulated some 150 years ago (Harris, 1998) by two students of Johannes Müller, botanist Matthias Jakob Schleiden (Schleiden, 1838) and zoologist Theodor Schwann (1839), plant and animal cells have been perceived as leading a double life (Schleiden, 1838).One living expression is devoted to survival as elementary and semi-autonomous organisms, and another serves as the essential building block of all multicellular organisms that must act as coordinated wholes (Reynolds, 2007(Reynolds, , 2008a(Reynolds, , 2008b)).Following this early conceptualization, Rudolf Virchow and his student Ernst Haeckel viewed all multicellular organisms as a form of cellular state in which every cell represented one individual citizen within a multicellular social colony (Reynolds, 2007(Reynolds, , 2008a;;Sander, 2012).In this Cell Doctrine, essentially autonomous cells link together to generate multicellular organisms yet maintain their individual priorities (Arias, 2023).This Cellular Doctrine was later replaced by the Organismal Doctrine stating that the entire multicellular organism comprises primary producing interdependent and subordinate constituent cells (Korn, 1999).Within the CBC model perspective, the Cell Doctrine is obviously the winner, although some aspects of the Organismal Doctrine are also relevant in the form of feedback from the higher levels of biological organizations.In some sense, these can be considered bio-environmental influences: the bodies of multicellular organisms represent the environment for their constituent cells.This intimate set of feedbacks and reciprocations among individual cells is essential for eukaryotic multicellularity (Arias, 2023) in which there is no specifically privileged level of causation (Noble, 2012).Within Cognition-Based Evolution, all biological and evolutionary development results from mutualizing reciprocations across all scales (Miller, 2023).We will discuss these important aspects in the following sections.

Hierarchical assembly of multicellular organisms: from protozoan-like cells to tissues, organs and whole bodies
In the evolution of multicellular organisms, cooperating sentient eukaryotic cells -which are already composed of several entwined sentient prokaryotic cells -evolved true multicellularity through sentient cell-cell communication and integration.According to the CBC theory, cells assembled supracellularly organized cellular files, some of which formed tissue-like epithelia, making a supracellular border that delineated the individual organs and the entire multicellular organism from their respective environments.As suggested for the first time by Ernst Haeckel, the embryology and development of multicellular organisms continuously recapitulate some developmental features that continue from ancient evolutionary times when the first eukaryotic cells embarked on the evolution of multicellular animals and plants forward to today.A good example of the early versions of plants are colonies of Volvox algae while contemporary choanoflagellates are considered to be very close to the most ancient animals (Baluška et al., 2023a(Baluška et al., , 2023b)).Critical issues in the evolution of multicellularity were the development of cell-cell adhesion molecules and cell-cell channels originating in prokaryotes, versions of which can still be found in all currently existing types of multicellular organisms, including complex fungi, animals and plants.These cell-cell adhesion domains and channels play important roles in cell-cell integration and communication (Arias, 2023).The reasons why ancient unicellular eukaryotic organisms joined forces to generate more complex multicellular organisms are difficult to illuminate, but predatory and collaboratory activities might be some of the critical issues.Yet, despite the success of eukaryotic multicellularity, many unicellular eukaryotic organisms still exist and are very successful in their survival and evolution in the form of diverse protists and algae.

Every eukaryotic cell is endowed with a dual version of cellular sentience due to the protozoan-like nature of all eukaryotic cells
In plants and animals, both of which represent true, complex multicellularity, sex cells fuse together to form fertilized zygotes which then divide through mitosis and produce all the cells of these organisms.Notably, these sex cells resemble contemporary protists with opposing lifestyles: amoeba-like oocytes and flagellate-like sperm cells.These sex cells differ in the major features of their cytoskeleton: the non-motile oocytes are based on an actin-based cytoskeleton, whereas the motile sperm cells are propelled by their flagella based on a microtubular cytoskeleton (Baluška et al., 2004a(Baluška et al., , 2004b;;Baluška & Lyons, 2018, 2021;Baluška et al., 2023aBaluška et al., , 2023b)).Intriguingly, all cells of animal and human bodies are represented by similar two major types: cells equipped with flagella that have modified into cilia protruding from cellular surfaces (Moran et al., 2014) representing most of our cells, including all epithelial cells and neurons (Croft et al., 2018).Other cells are devoid of flagella and resemble amoeba such as all cells of the immune system.Consequently, our body cells continue to display their protozoan character (Baluška et al., 2023a(Baluška et al., , 2023b)), supporting Rudolf Virchow's concept of the autonomous cell-like character of multicellular organisms in which individual cells are analogous to citizens of our human societies (Reynolds, 2007(Reynolds, , 2008a(Reynolds, , 2008b;;Arias, 2023).In the past century, these prescient ideas about the protozoan nature of all eukaryotic cells were discarded as irrelevant (Richmond, 1989;Reynolds, 2008b).Nevertheless, they should be revived and discussed from the perspective of new findings that amply confirm that cells are self-referential cognitive and sentient agents and capable of complex patterns of cell-cell communication (Shapiro, 2021;Reber et al., 2023;Arias, 2023).All embryogenesis and the development of multicellular organisms emerged through processes based on cell-to-cell communication that supports the hierarchical cellular assembly of diverse tissues, organs and whole bodies of all multicellular organisms (Lyons, 2020;Arias, 2023).
Consequently, a coherent cellular narrative can be presented.The protozoan-like basis of all cells in multicellular organisms starts with the sexual fusion of amoeba-like oocytes with flagellate-like sperm cells.As noted previously, these cell types can be distinguished through their differing cytoskeletal characteristics, primarily actin-based in oocytes and tubulin-centrin-based in sperm cells (Baluška et al., 2004a;Baluška & Lyons, 2018, 2021;Baluška et al., 2023aBaluška et al., , 2023b)).Furthermore, the most important cellular processes for embryogenesis, organismal development and evolutionary development depend on actin-based cytokinesis preceded by tubulin-based mitosis of the nucleus.These two processes can be uncoupled so that mitosis is not followed by cytokinesis.This supports the inherently dual nature of the eukaryotic cell (Baluška et al., 2004a(Baluška et al., , 2004b) ) and corresponds to the duality of its evolutionary origin.We propose further: eukaryotic cell sentience is also dual, composed of the actin cytoskeleton/membrane sentience of the host cell and the tubulin-based cytoskeleton/membrane of the guest cell (nucleus) that together merge into a seamless whole as a fully integrated eukaryotic cell.

Cellular and vesicular communication in the physiology of multicellular organisms
As we have discussed extensively in our recent book The Sentient Cell (Reber et al., 2023), cellular sentience is based on excitable biomembranes and cytoskeletal elements.Cellular organelles are of endosymbiotic origin and communicate within all eukaryotic cells via diverse vesicles and intracellular synapses (Baluška & Mancuso, 2014), which integrate originally independent prokaryotic cells and their senomes into coherent eukaryotic cells with a chimeric senome.By this means, cells of dual origin can coherently engage environmental information by the melding of their senomic apparatus effected via an overarching N-space episenome that supports conjoining multicellularity.Thus, the supracellular-based N-space episenome constitutes a surrounding information field whereby all cells, tissues and organs experience interpretable electric fields and clouds of ionic molecules and reactive molecular species.
In some sense, cells are bioelectric systems due to their limiting and excitable plasma membrane separating opposing electric charges inside and outside of cells which represents a bioelectric insulator.Moreover, the cytoplasm has also a bioelectrolytic nature.Frances Ashcroft calculated that half of the food we eat is used to maintain the ionic concentration gradients across the plasma membrane (Ashcroft, 2012).Accordingly, there are bioelectric fields around cells, tissues and organs that can be assessed via sensitive techniques such as vibratory electrodes, ECG and functional magnetic resonance imaging that take advantage of the fact that cellular bioelectric fields are summed together as composite values which can be measured and quantified (Ashcroft, 2012;De Loof, 2016;Tuszynski, 2019;Kwon, 2023).All cells, tissues and organs communicate with one another and integrate into coherent bodies via bioelectric fields and extracellular vesicles (Baluška & Levin, 2016;Levin, 2023;Reber et al., 2023).The extracellular vesicles integrate diverse organismal kingdoms into supra-organismal unity (Lynch & Alegado, 2017;Woith et al., 2019).As extracellular vesicles are generated by all cells (Deatherage & Cookson, 2012) and the vesicle is the most simplified proto-cell (Reber et al., 2023), it can be proposed that the extracellular vesicles represent the most ancient vehicle for cell-cell communication.
Extracellular vesicles act as messengers in cell communication and are an important additional aspect in our understanding of cell-cell interactions (Hanayama, 2021).These vesicles are relevant not only for whole organismal physiology but also because they participate in almost all known disease processes (Iraci et al., 2016;Saheera et al., 2021;Salomon et al., 2022;Liu & Wang, 2023).Furthermore, the release of these plentiful extracellular vesicles is obviously an ancient feature with ecological relevance since they are present not only in all eukaryotic cells, but also in archaea and bacteria which release vesicles for the exchange of diverse molecules and for cell-to-cell communication (Deatherage & Cookson, 2012;Hasegawa et al., 2015;Akbar et al., 2019;Toyofuku, 2019).In some sense, vesicular trafficking between organelles of eukaryotic cells as intracellular and cell-cell communication are vestiges of their origin from originally free-living prokaryotic organisms.Given these primordial roots, and even when fully integrated within the eukaryotic cell, each cellular participant in multicellularity is a full participant in the whole while still maintaining partial cognitive autonomy permitting independent decision-making.This is not conjectural.All the information that any cell has is a product of its senomic apparatus.For multicellular organisms, all of their environmental information is necessarily experienced at the level of each individual cell.Only action at the cellular level permits the mobilization of cellular resources to the multicellular organismal entirety (Miller et al., 2020a(Miller et al., , 2020b)).Consequently, the eukaryotic cell can be considered a nexus within a system of nested cognizers.These cell-like sentient subsystems start at the subcellular level as symbiotic organelles, which derive from prokaryotic unicellular roots, and reach up across tissue, organ and organismal levels to create fully integrated holobionts.
Extracellular vesicles in the cognitive immune system are a form of cell-cell communication that participates in defending the self and bacterial antibiotic resistance Besides the already mentioned diverse roles of extracellular vesicles in cellular, tissue, and organ communications and interactions, current scientific studies indicate that these flexible vesicles have an essential role in self/non-self recognition by diverse immune cells (Del Vecchio et al., 2021;Dosil et al., 2022;Georgatzakou et al., 2022;Matsuzaka & Yashiro, 2022;Kim et al. 2023).Particularly intriguing are immune synapses between T cells and antigen-presenting cells in which micro-villi-like protrusions mediate communication and recognition through the release of specific extracellular vesicles termed T-cell microvilli particles (Kim & Jun, 2023;Kim et al. 2023).Finally, vesicles released by bacteria serve not only for bacterial communication but also in mediating the transfer of their antibiotic resistance (Chattopadhyay & Jagannadham, 2015;Uddin et al., 2020;MacNair & Tan, 2023).As vesicles represent the prototype of the most ancient cells (Reber et al., 2023), it is perhaps not surprising that they are also used as a kind of universal messenger (Deatherage & Cookson, 2012;Lynch & Alegado, 2017;Woith et al., 2019) for inter-organismic communication.

Cellular pathology and aberrant cell-cell communication
We urge a return to Rudolf Virchow's far-sighted view, expressed in his book Cellular Pathology, that all illnesses and diseases have their ultimate origins in diverse pathological changes within cells (Virchow, 1878).This should not be surprising since all multicellularity is centred within cell-cell communication, cognition and cellular sentience (Baluška & Reber, 2019;Reber et al., 2023;Mukherjee, 2022;Miller, 2023).To achieve a full understanding of the diseases which plague humanity, we must look to cells (Nurse, 2000(Nurse, , 2020;;Mukherjee, 2022;Reber et al., 2023;Arias, 2023).Their structural and physiological aberrations result in pathological cellular sentience and cognition, triggering deficiencies in cell-cell communication that impair immune responses and cellular repair.This disruption in cell-cell signalling among cognitive cells represents the true source of most pathological problems emerging in our bodies as physiological breakdowns sufficient to yield illness and disease (Torday & Miller, 2020).
There are two examples of pathological situations resulting from the mismanagement of cellular communication which cause serious health problems.One is cancer in which cells fail to maintain proper development and morphogenesis in our adult bodies.Another example occurs in endometriosis when endometrial cells escape from the uterus and invade other tissues and organs of women's bodies.Both cancer and endometrial cells construct aberrant organs functioning as tumours and endometrial lesions (Albini et al., 2010;Anderson & Simon, 2020;Bożyk et al., 2022;Chen et al., 2023).This is most dramatically illustrated, albeit rare, when endometrial cells transit up to the brain, invade the cerebellum and trigger ectopic endometrial lesions (Sarma et al., 2004;Elefante et al., 2022).It can be speculated that tumours and endometrial lesions represent aberrant attempts at organogenesis, perhaps constituting deviant forms of failed embryogenesis and development.Intriguingly, extracellular vesicles released by tumour and endometrial cells play important roles in both cancer and endometriosis (Freger et al., 2021;Huang et al., 2022).

Coda
An understanding of all cells as sentient and cognitive living systems is essential not only for our understanding of life as a whole but also for dealing with diseases that have their roots in cellular physiology (Mukherjee, 2022;Arias, 2023).However, old ideas still circulate that inhibit progress.In a recent highly successful book, Immune: A Journey into the Mysterious System That Keeps You Alive, which was notably advertised and promoted in the prime science journal Science, the German Youtuber Philipp Dettmer (Dettmer, 2021;Davis, 2021) declared that cells represent mindless robotic automatons.In his chapter 3, ʻWhat Are Your Cellsʼ, Dettmer blithely states that the cells of our bodies are mindless robots that are nothing but bags of proteins guided by chemistry (Dettmer, 2021).There is a grave misunderstanding of the immense complexities of cells (Nurse, 2000(Nurse, , 2020;;Mukherjee, 2022;Arias, 2023) which embody the essence of conscious self-awareness and cognitive and sentient competence (Lyon, 2015;Lyon et al., 2021;Shapiro, 2021;Reber et al., 2023).This seriously misleading but sadly prevalent view of the actual capacities of cells is a critical disservice to both the scientific community and the general public.It also seriously undermines opportunities to explore and exploit the prodigious capacities of all the cells of our bodies that connect us (Slijepčević, 2023) to our living planet.