Conceptual cells

What cell-to-cell communication teaches us about human society

Federico Germani

Federico Germani

Federico is a passionate and enthusiastic bioethicist and molecular biologist at the University of Zurich, Switzerland. He is the founder and director of Culturico. He brings awareness to the broad public of how the scientific publishing system works. He believes in multidisciplinary approaches, as opposed to narrow-minded – limited – ways of looking at reality. This is why he reads and writes about topics ranging from science to international relations, and from society to philosophy. Twitter @fedgermani

Cells interact with each other in different ways, by direct contact or by releasing specific molecules to elicit a biological response in target cells. Communication between cells guarantees the successful functioning of the organism. In this article we analyze how this precise and successful cellular communication strategy differs from the way humans communicate in society, which may serve as an intimate explanation for our failures in functioning as a cooperative society.
 
Cells, the building blocks of living organisms, are able to communicate with each other predominantly using three different strategies: juxtracrine, paracrine and endocrine signaling.
When adjacent cells are in contact with each other, they communicate through components of their plasma membrane, the complex protective layer that surrounds each cell. This particular strategy is termed “juxtacrine signaling(1).
Alternatively, cells can secrete molecules that act as signals targeting neighboring cells. This type of communication, called “paracrine signaling”, includes for instance neurotransmitters – which are vital for us to perceive the surrounding environment, feel pain and think rationally. Other well-known signals include estrogens, which are locally produced by the ovary. Cells can also induce a response in their neighbors by secreting cytokines, which are molecules necessary to elicit an immune response.
When these molecules are released into the bloodstream and act as long-range stimuli, we classify this type of communication as endocrine, and the secreted molecules are generally referred to as hormones.

Cells may be sensitive or insensitive to certain stimuli. As we have seen, released molecules are a preferred way for cells to communicate. To simplify the concept, ligands can interact with specific receptors similarly to the way a key can access its specific lock. If a target cell does not possess a receptor – it is not receptive – for a certain ligand, the cell won’t respond to the stimulus. However, if a cell exposes the receptors on the plasma membrane, ligand-receptor interactions will lead to the activation of a signaling cascade, which is a sequence of chemical reactions between proteins within the cell that eventually leads to a biological response (2).
Possible biological responses include programmed cell death, which is called apoptosis, cellular division, cellular movement, or the production of other molecules.
In other words, a cell can signal to another cell to act in a precise, timely and accurate way to perform a certain biological task, including cell suicide.

Given the existence of various subcellular types, these highly specialized entities are able to collaborate with each other, allowing for the proper functioning of the whole organism. Without cell-to-cell communication, an organism would simply not exist.
For most readers, it may seem counterintuitive that inducing the death of a cell would have a positive effect for the health of the organism. In certain tissues like the intestine, cells constantly regenerate, and as they grow old, their capacity to perform certain tasks decreases. In order to keep the system running efficiently, the organism carries a population of stem cells that constantly replenishes the tissues with new specialized cells. Replacing old cells is important to keep the system efficient by preventing the formation of cancers, as older cells also accumulate more mutations over time (3).
Another great example of why apoptosis is necessary and fundamental comes from our time spent in the womb. During limb development, massive cell death occurs to sculpt the shape of the limb and to form digits (4). Without apoptosis, we would be born with deformed limbs.

Cells use mechanisms of cell-to-cell communication also to compete with each other. This process has been termed “cell competition(5).
As we discussed, cells within tissues are in constant interaction with each other and sense each other’s presence. When a cell acquires specific mutations though, other cells may push them to die. Although the intricate nature of this process is currently being debated in the “cell competition” field (6,7,8), the mechanism is highly conserved and comes with biological relevance. It is believed that such mechanisms could be used to prevent dangerous, mutant cells from acquiring secondary mutations that can transform them into malignant cancer cells (9). Once surrounding cells detect an issue with their neighbor, they may release signals that impose death on the “loser” cell.
 

Cells-that-Race-and-Dance
Conceptual cells – Image credits: Truth seeker

Biology has selected mechanisms for cells to cooperate, compete, and die if they are required to do so, and the existence of such layered communication is what maintains a functional organism.
Cancer constitutes an exceptional case. Although all these prevention mechanisms are in place, cells may acquire spontaneous mutations that cause them to become carcinogenic.
Cellular life is a highly cooperative society with a defined structure, in which life is limited to functionality. When the function of an individual cell in the micro-society is not required, its life is normally terminated.
A cancer is instead a non-cooperative system that is generated spontaneously within a cooperative one. Cancer cells become individualistic and enhance molecular mechanisms to escape cell death and proliferate indefinitely.

Similar to the micro-world, life on Earth is structured and functional. Ecosystems adapt to the environment, and each individual component guarantees the existence of the planet as a whole.
However, humans have spontaneously acquired characteristics (i.e. advanced intelligence, an adaptation analogous to a “mutation” in the cellular dimension) for which we attempt to escape death by prolonging our lives through the use of medicines, thus establishing a non-cooperative system. For a detailed discussion on this topic please read the article entitled “Humanity is a cancer”, where we dissected and described these characteristics, or mutations, that define us as a cancer for our world.

Human society can be considered somewhat as a fluid entity between a cooperative and non-cooperative system: we belong to nature, and as such, our intimate essence is to be part of a cooperative system, like cells are. We struggle to survive, and compete with each other and with the external world. Like all other animals, we live within our world, we are bound to it in our daily lives. Though, because we are highly intelligent, we also live outside of the world – we think about our own existence and the world we live in – and have acquired ways to cooperate with each other that override our animal, natural instincts.

Our natural cooperative component does not disqualify us from being considered as a cancer for the planet, as tumors are heterogeneous in their nature. Some cells will show a more aggressive behavior and others will remain partially or completely sensitive to signals released by other cells. Some will become invasive and some other will remain benign. This means that cancer cells, as we do in our dimensional reality, also live within and outside of their micro-world. And the heterogeneity of human behaviors, from highly cooperative to hostile and dangerous, simply represents the spectrum of our deranged, carcinogenic, society.

Therefore, is reasoning, thinking and reflecting in the way we do something that fosters cooperation? In other words, is advanced intelligence a cooperative trait?
In a “natural” sense, probably not. Questioning our existence, posing ourselves questions that transcend our daily lives, are all fundamentally minimizing our chance of being cooperative elements within our species and among species, in harmony with the environment that surrounds us.

If you are still unconvinced, here is how a natural, cellular cooperative system would behave.

Competition between individual cells, and the elimination of the less fit (cell competition): although humans have maintained competitive traits, human society has dragged humans out of natural competition, by establishing laws and rules that individuals have to follow. Cooperative competition, – the Hobbesian state of nature (10) – is therefore lost.

A chain of command, in which each event triggers another one: cells live in a hierarchical society, based on sectorial competences. Our human society is also based on sectorial competences, but with the additional presence of an overarching societal structure in which non-experts are allowed to make decisions. In a dictatorship a single person has decisional power over a multitude of things they don’t necessarily know much about. In a democracy, a multitude of people can take direct or indirect decisions – through referenda or elections – on issues they are not competent about. If our society would be naturally hierarchical, people with specific knowledge would take decisions within their area of expertise (for instance, civil engineers would define themselves a plan for their city, without consulting anybody else ­– and imposing their decision). Basically, an undemocratic system.

No attempt to live forever (except cancers), or to elongate lifetime over function: cells accept they have a natural fate, we don’t. Why? Because we don’t know what our natural fate is, and we pose ourselves existential questions. A cell wouldn’t pose such questions, and even if it would possess advanced intelligence it would not be able to understand that its function is to make the organism work properly. It follows that if human society would be a naturally cooperative one, there would be no production and no use of any medicine (unless readily available in nature). We wouldn’t fight the biological clock that nature has imposed on us with its laws.

Basically, to establish a truly (naturally) cooperative social system, we would need to give up what we feel makes us human in the first place. As nobody wants this, we probably need to follow the opposite path. Instead of reverting to the state of nature, we should enhance our thinking skills, our intelligence, to one that critically understands the needs of each individual human being, but at the same time considers the relevance of the system we are part of. We should think of what our intelligence, our thinking, means for our society and improve it: this fluid, intermediate condition we are currently playing a part in is destroying the planet, and ourselves, like a cancer.

 

Federico Germani

 

References:

  1. Gilbert, S.F., “Developmental biology”, Sinauer Associates, 2000.
  2. Cantley, L.C., et al., “Signal transduction: principles, pathways, and processes”, CSH Press, 2014.
  3. Risques, R.A. and Kennedy, S.R., “Aging and the rise of somatic cancer-associated mutations in normal tissues”, Plos Genetics, 2018.
  4. Chen, Y. and Zhao, X., “Shaping limbs by apoptosis”, J Exp Zool, 1998.
  5. Amoyel, M. and Bach, E.A., “Cell competition: how to eliminate your neighbours”, Development, 2014.
  6. Germani, F., et al., “The Toll pathway inhibits tissue growth and regulates cell fitness in an infection-dependent manner”, eLife, 2018.
  7. Alpar, L., et al., “Spatially restricted regulation of Spätzle/Toll signaling during cell competition”, Dev Cell, 2018.
  8. Nagata, R., and Igaki, T., “Cell competition: emerging mechanisms to eliminate neighbors”, Development, Growth & Differentiation, 2018.
  9. Di Gregorio, A., et al., “Cell competition and its role in the regulation of cell fitness from development to cancer”, Dev Cell, 2016.
  10. Hobbes, T., “Leviathan”, 1651.
Received: 13.11.19, Ready: 01.01.20, Editors: BK, RG.

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