II

LET’S START AGAIN: LIFE

Uncertain, rough, jagged and confusing is the border between life and soul.

Still, their different matter is evident. It is easier to deny a machine a “life” ‐ a feature that even the most stupid worm or thread of grass possess ‐ than the possibility of a soul. Robots and spaceships in science fiction do not live, but some of them have been capable of suffering and desiring and dreaming and loving.

To preserve a minimum of scientific dignity some definitions must be crystallized, some scaffolds erected to try and look farther. So, let’s fix some definitions, let’s draw some clear limits.

Let’s forget, for a moment, our life, life as history, life as memory. And let us talk about “life” ‐ bios ‐ the life of biologists, theologists, cosmologists: where there is life, and where there isn't, what makes the difference between a living entity and an inanimate one, how life begins and how it ends. Pretty light and easy questions...

In this world it is possible to persist, or survive, or live. Structures and objects, up to a certain degree of complexity ‐ wonderful crystals of purple quartz ‐ reach a stable equilibrium, each molecule resting as comfortably as possible, nobody nervous, no energy to give away. Cold. Dead. In the absence of external perturbations and forces these systems do not change, they exist and persist for ever. They may grow, sometimes, by engulfing in their ‐ senseless or wonderful ‐ dead organization new molecules, that they subtract to the external world, where life quivers. Sometimes they disaggregate, they get lost.

More dynamical and complex structures are sustained by unstable balances, that are not «equilibrium». Static appearances with no peace, they survive thanks to forces that corrode and nick and change them, but they can change so skillfully that they dissipate the forces that undermine them; they even exploit the energy that comes from this dissipation to repair, regenerate and perpetuate ‐ as long as it is possible ‐ the features that define their fundamental nature, and to reproduce their own equilibriums, i.e., to reproduce themselves by generating living «copies» of themselves. This is the main feature of biological systems: they are dynamical systems that maintain their integrity and evolve during their life by means of complex processes of regulation of their internal parameters, and of a continuous interaction with the external environment. This is what we can rigorously call «life».

An aspect may help better than others in clarifying the difference. Left alone, a crystal does not change, and persists. Conversely, with no interactions with the exterior, with no forces that try and change it, with no exchanges to gain energy, a living being nevertheless does change, but does not persist, does not survive, it degenerates and dies. It cannot survive without nteracting with the ouside world. It is a fragile and demanding balance. Like a music that appears to develop and continue in an admirable equilibrium of vibrations, but wanes into echoes if one stops singing, and dies in still air.

What, then, sustains life?

What force pushes the living organism to continually fight to survive and repair the damages of time and rebuild, moment by moment, arduous balances, and reproduce itself and proliferate?

Physico-chemistry, in principle, is not complex. It is like running a nursery school. A number of hyperactive children: they run, jump, scream, they chase one-another, flounder and turn around. If you organize them in such a way that they have room, distractions, amusements, and the possibility of settling down in any imaginable new way, of saying and doing what they want, then it is more likely that they will not run away or destroy everything. Also, it is less likely that they will build something, or efficiently perform some work...

The question is energy. The more they waste in running and playing (hell, this is what always ruins us, post-catholic thinkers: who says that this is wasted energy, who says that only the energy that is used to work is good, well spent?), the more energy they devote to move around and play, the less they will have to build or destroy, inside or outside the school.

Atoms and molecules are admirable equilibriums of ridiculously small matter particles and huge energies. They get closer, match, combine and move apart. The more the electrons are at ease in a molecule ‐ wide paths for them to run around, some beloved protons at reach, other electrons out of the way ‐ the more they will be able to shake and play, without disturbing the general balance; also, it is unlikely that they will perform a work, by running away and moving or hitting and modifying other molecules.

The same is true for big molecules, such as proteins. They are at ease when their regions can turn around and resettle, graciously combining among themselves, the electrical charges well organized, water molecules trapped where they fit well, hydrophobic regions in reciprocal contact... Portions of the molecule that wish to rearrange and explore other positions can do it without compromising the general structure, and the protein is well and stable.

But if the possibilities of rearranging and changing position are limited, like when one sleeps on a chair, or a hard and narrow couch, sooner or later the equilibrium breaks down, the protein changes its form, and interacts with other substances.

Mathematics, as usual, can tell it precisely. The more numerous are the ways a system can rearrange in (states or conformations), the more energy is spent in this babbling: it is energy that faces inward, entropy ‐ yes, let’s say it, entropy, although it is an arcane word, that repels most people who encountered it, and hope nobody will ever ask them about it.

The more energy faces inward, the less can be given away to perform external work: so, less is the “free energy”, energy that can perform work. The equation is precise, and is one of the most general equations in physics. The probability that a system rests in a certain conformation is proportional to the number of states that this conformation admits ‐ like playing the roulette: only one good number, 36 losing numbers; either the wheel is deceitful or most of the times a losing number will come out.

Probability. And entropy is proportional to the logarithm of probability. Mathematics tells us how probable it is that a system rests in a particular state, and such probability tells us what part of the energy associated to the system is entropy, and cannot be used.

Entropy reflects probability, disorder ‐ did it ever happen that something reordered itself on its own (one ordered conformation versus innumerable disordered ones)? It reflects the ease for electrons, molecules, forces and relations to fool around without “producing damages”.

Maybe, happiness itself is a metaphor, or even a form, of entropy. The possibility of discharging energy, pursuing desires, expressing wishes and finding oneself with no need to change modes and situations. Actually one consequence of this is that those who are too happy get drowsy and dull, and may lose the drive to do and build, even to merely preserve happiness.

However, “happiness” is a heavy word. One should be more cautious: well-being, maybe. Happiness is something more. But how much more, why more? to be, not to be, to die, to sleep, perchance to dream...

But it is not time for this, yet.

Time is abstract. As such, it has its meter. It is absolute distance, and relative. Past and future are far away and equally remote.

But the time of things has a direction.

The time of things erodes, smoothes, corrodes, disintegrates.

It does not create. It cannot. It does not move backwards.

And it plays the role of an inexorable force of nature and matter.

But not even time is omnipotent. It only erodes and disintegrates what lets it do it.

A force is needed, possibly the slightest gust of wind, to upset even the weakest and most unstable balance, even if it is ready to ruinously break down. The time of things is powerful, but it cannot start its own job by itself. It is blocked, it just watches and waits, until something impairs the balance; then, time breaks in, efficient, rapid or quiet, but inexorable. It dismantles. Until a new balance is reached, be it necessary or fortuitous, be it greatly or only slightly more stable. Then, time gets back to its patient waiting for another cracked balance that it might upset.

Think of a card tower. It could rest there for eternity. A slight shake, and it breaks down. You can make it more accurate, solid, ingenious. It may still break down, but it will take a stronger shake.

Here is the law of time. And of physics and chemistry. Often, improbable orders and equilibriums would wish to break apart but they cannot; it is called potential energy, ready to be set free, as in a match, or in a bomb. On the other side, there stand brakes, limits and restraints, that must be cracked for order to disperse and vanish; we call it activation energy, the energy that must hit the house of cards in order for it to fall down, or hit the bomb to make it explode.

Everything whirls and vibrates in the world of matter. Temperature is but a measure of molecular frenzy. Give it some heat, the temperature rises, every molecule vibrates more; each atom twirls to snake out of the molecule that traps it; each electron, proton, neutron bites more strongly the brake that binds it to its atom. For each intensity of a shake, only some card towers are possible. For each temperature only certain molecules and atoms are possible: only those where attractions and brakes are stronger than frenzy.

And time is there. It peers, ready to break in and destroy impossible and cracked castles.

Just after the big bang, while the universe was cooling down, in the first moments of its billions of years, the inert matter clotted on each single possible shelf of the chemical vocabulary, like snow on the branches of the trees. As the temperature decreases, the 'freedom' of the atoms diminishes and they settle into larger molecules. Like snow, ready to fall down at the first blow of the storm or at the fist bump of an unskilled skier.

Sunrays arrive to the earth. Everything could warm up slowly, and matter could experiment new instabilities and balances. Just like the snow, thrown up again in the air by the storm. Thereafter, some million years later, the sun getting old and weakened, everything would cool down again, the storm would gradually wane. The same snow would not be on the same branches, but some snow would still be on the branches, just like before. And everything slowly getting colder, quiet, coagulated, still and immutable.

Poor time! with all its eyes and tricks it cannot make sure that each snow flake finds its way down to the ground, as long as the wind is blowing. And when the wind calms down, it is too late, nobody is there to crack the unstable balance of the flake, at the border of the branch, to let it free to fall down to the ground. Time cannot make sure that each atom, each electron escapes soon enough from fatal attractions, that it finds its best environment so that it will eventually be happy; once the frenzy has cooled down, they will no more hasve the energy to disengage from unlucky, fortuitous and gloomy restraints.

Tasteless history of matter. Senseless and wonderful in the evocative games of stalactites and stalagmites, in admirable quartz crystals, in the astonishing ambiance of the grand Canyon, in the charm of a crystalline water spring...

* * *

Here they are, chemistry and physics...

A world of constrained order. Ready to fall apart if only someone helps to. Someone clever enough, maybe, to use that same energy, which a blocked order releases in breaking down, to crack other balances, other orders that may also disaggregate. It is like a line of dominoes, that stand up and wish they could lie down, if only someone gave them the kick that is needed: the slight, gentle touch that unbalances just one of them. In losing its balance it releases the energy that is hidden in its standing up, smashes down the second domino, this does the same to the next, and so on for all the others.

A world of constrained order. And possibly someone so clever to guide the production of disorder, the release of hidden potential energy, maybe even so clever ‐ alive! - not only to do that, but to use that same energy to build, and maintain, and strengthen and reproduce its own order, that could not exist and persist with no care and maintenance and repairs, its own life.

Among the possible equilibriums experimented by matter, there is a class of intriguing molecules: RNA, a type of nucleic acids. RNA is a well designed balance of smaller molecules ‐ a sugar, a base, two phosphates ‐ linked in long twirled chains. A revolutionary equilibrium, because it favors the coming close of other sugars, bases and phosphates, which orderly adapt on its blueprint and produce a perfect replica, a new identical chain (more properly, a symmetrical, complementary chain, but that makes little difference). The molecules that constitute RNA can stay perfectly well by themselves, but if they approach an RNA chain already formed they are subjected to strain and attraction, that may crack their small card tower, blow it up and let it settle down into a more complex and stable house of cards: a new chain of RNA, complementary to the first one and mirroring it.

Certainly this is not life, yet. But of life itself this recalls a crucial aspect, the capacity and tendency to reproduce itself. And, even more important, the capacity of exploiting the energy hidden in relatively stable, restless molecules and calm them down into more complex structures, into higher orders.

ROS: Reactive Oxygen Species. Free energy (too free?...) that sustains life.

Oxygen is life. Because it is eager for electrons.

He who is truly alive is equally eager and greedy for emotions and ideas.

Without oxygen each molecule in an organism would rest quiet in a deadly inertia, and I would boil the same usual thoughts again and again.

But the puzzle of life, with its chaotic, unexpected and complicated matches, is never complete. It is renewed and reborn at all times, by continuously rediscovering already experimented combinations and inventing new, improbable equilibriums. Because there is no rest. Because oxygen chases and requires electrons, it asks for answers, and questions, agitates doubts and proposals, novel readings, possible metaphors and audacious flights.

The cell breaths by stealing electrons and protons to sugar ‐ which is thus dismantled until it vaporizes into sterile carbon dioxide ‐ the same way we steal images and sensations and emotions to the world. The cell cautiously handles these electrons, one by one, to the greedy oxygen, while protons are spun and shuffled around until they can get married, in the end, to the oxygen so charged, thus yielding placid, stable water molecules. The cell lives by accumulating the energy that uncertain and reactive compounds release in calming down into solid unions. Energy and tension that fosters the continuous remodeling of the cell, tension that moves us and forces us to continuously reread and revisit, and to try and continually rewrite, reality and life.

Alas, precisely because of its sacred and compulsory avidity and vitality oxygen sometimes runs away with an extra electron, unpaired and explosive. It runs away alone, or together with the atoms it stripped it from, or with others that enjoy sharing the daring instability of the single and turbulent electron, of the unfulfilled emotion, of the barely imagined thought, incomplete, unfinished and infinite.

They call them ROS, reactive oxygen species, they call them radicals ‐ free, vagabond, reactive, boisterous, out of control.

Indispensable, to attack snobbish and apparently incorruptible molecules, that must anyway be dragged, them too, in the continuous merry-go-round of biochemical dances, a process that moment by moment rearranges and rebuilds immutable, ever-new and ever-changing equilibriums.

Indispensable, but they may spoil and harm. They may crack and demolish antique, delicate balances. And other electrons are needed, other stimuli, and emotions and affects and ideas, to calm them down, so that unpredictably balanced, new combinations of forces and masses may happen, and transform, dance, live, rather than collapsing, disaggregating, leaving the game and dying.

A thousand substances, continuously renewed and gathered from outside, protect the cells, by donating their electrons to radicals that have gone mad. They are called antioxidants. A thousand policemen and teachers and mercenaries and clowns and poets offer you rules and lashes and punishments and smiles and emotions to calm you down when the soul breaks apart and energy does not find a way out. Often, a harmed soul can sooth another one, often ROS can pacify each other by sharing their injured electrons.

Neurons, brave cells, noble and selfless, hyperactive in taking note of the history they see and live, by translating it into ever-new reorganizations of their biochemical and functional balances; neurons, that because of this are unpredictable cells, more difficult to protect, sometimes can’t face the tension of a life made of continuous asking and retrying and going back over, a life full of storms and raids of molecules gone wild. So, neurons get old. Mechanisms of admirable efficiency and precision may get oxidized and misfire. Thus, any tiny defect gets amplified. Serious, efficient, reliable proteins miss their duties, are secluded and start to die: aggregates appear that reveal neuronal suffering to the pathologist, as the unequivocal signs of diseases with terrible names, Parkinson, Alzheimer...

But there is no Evil. And Good.

There is only Life.

It is a challenging bet, hard and demanding, that turns out winning an incredible number of times, and is promptly renewed, continuously, always on the edge of a shaky balance, lost and regained. ROS, wild thoughts and wounds of the soul are not demons, they are sublime forces that move the world, and they can hurt because they don’t know how to sit aside and just watch.

Free radicals damage the skin, antioxidants protect it... But radicals are nothing but moments of life, and our vegetables, and drugs, and vitamins, are not capable of shutting them up to protect the skin that needs most their uncontrolled vitality, and some protection from their excesses: neurons, the skin of the soul.

And if the whirls of the soul damage the quiet management of society, without them there is no life. Let them anti-oxidize us as they wish! as long as in the world there is injustice, and hunger, war and pain, there will be sympathy, surprise, desire and love, and there will be curious souls, wounded, tense, lighted. There will be life.

But that’s enough with games.

What is life, in the end?

Life is a principle, abstract as you wish, that differentiates the systems that persist quiet, as long as external forces don’t put their balance at risk, from those systems that instead can only survive by means of interactions with the outside, and are sufficiently complex to be able to exploit external sources of energy to reproduce moment by moment their own structure and organization, their shaky and mutable balance, and capable of reproducing themselves by regenerating that same order, that same organization, in new exemplars.

Life is a well conceived mechanism that sustains and reproduces itself by guiding chemical reactions that release energy, by helping the sun to build ‐ rather than merely and stupidly heating the Earth ‐ new unstable balances, and by helping time, who could not by itself attack them, to crack and dismantle them. Life is a one-way road that allows the second principle of thermodynamics to come true: it allows entropy to grow under conditions where it would not find its way by itself, it allows the time of things to flow more free and powerful.

Indeed, life is not abundance of resources and room to throw away garbage, but rather the admirable capability of transforming resources into garbage, of producing disorder, while pursuing a project. Maybe, more simply, it is the project itself.

One survives by protecting himself, but one lives by changing in the “tourbillon de la vie”. Life itself is nothing but a “way”. Life is real, but its reality consists in the “way” the living being is. You need a name for this ‐ life, precisely ‐ and an ontological value: anybody would clearly perceive the absolute reality of life, thus defined.

But the question is exactly this: per se, life has no reality whatsoever, if by “reality” we mean palpable matter it is only an abstract concept. But life is real, ontologically real, as an immanent property, unavoidably inborn to the organism that possesses and expresses it.

Life is a physical mechanism, a organization criterion, an abstract principle. Form, that is not less real than matter, inherent in living matter, form that is physical and outside of Physics. Internal and going beyond. Metaphysical, indeed, exactly and precisely.

And if the most clever ones already got where we are heading ‐ and what has all this to do with the soul ‐ then they are kindly asked not to unveil the end to more peaceful and eager readers.

WHAT DO WE KNOW, IN THE END? ‐ Animal Neurophysiology

Some neurophysiology, at last! here I feel at ease....

Among those that are attracted ‐ by intellectual curiosity or by their study plans and duties ‐ to neurophysiology, a large majority comfortably lays down in the perspective that is widely supported by the lazy and little creative dominant mechanicism: the nervous system is a complex device, very complex, hypercomplex, god! how it is extremely complex!, but with a clear design principle: it is structured and organized to produce the right behavioral response to the stimuli that are present at any moment and in any situation.

Nice and clear, but then no surprise if one steps back, wrinkles his nose and says to himself “sure, but the soul is something else”.

Sure, the soul is something else. But the brain, man’s brain at least, is also something else!

Let us proceed with some order.

The nervous system

The nervous system is constituted by hundreds of billions of nervous cells (neurons), each of which in general exhibits a rich branching of thin processes (dendrites), on which tens of thousands of terminals from other neurons make contact. Such contacts (synapses) generate a small electrical signal, when they are activated, and all signals reaching a neuron get summated in space and time to generate a fluctuating electrical signal in the cell body of the neuron. Each time this signal trespasses a precise “threshold” value, a rapid potential spike is generated (a wave about 1/10 of a Volt high) where the principal process of the neuron (axon) leaves the cell body. When a neuron generates a spike, this is propagated by means of a regenerative process: it is identically reproduced in the nearby portion of the membrane and gradually invades all the axon, that can be a few millimeter long, but in some cases may reach tens of centimeters in length. The axon may branch close to its target and ends in small varicosities (nerve terminals) that contact other neurons (or muscle or gland cells) making synapses ‐ structures where the membranes of the two cells are very close: when the spike invades the terminal, small quantities of chemical substances (neurotransmitters) are releases, that are capable of generating on the target cell the small electrical signals discussed above.

Central Nervous System (CNS)

The great majority of neurons is located in the central nervous system, which is constituted by the spinal cord and the encephalon (the part located in the head). The CNS is constituted by groups of neuronal cellular bodies, dendritic trees, synaptic buttons and short local axons (the gray matter), and by bundles of axons that connect the gray regions; these longer axons are generally sheathed by an isolating material (myelin), that facilitates and accelerates the conduction of the spike, and are collected in bundles that are visible to the naked eye (white matter).

Spinal cord

All sensory information coming from a segment of the body ‐ from the skin, the joints, the muscles and the internal organs ‐ enters the spinal cord at the corresponding level, by means of axon bundles (nerves) collected in the dorsal nerve root. The neuronal circuits contained in the spinal medulla elaborate simple reflex responses (such as the patellar reflex that the neurologist tests by hitting your leg with a small hammer just below the knee); they simultaneously send all information upwards and receive control signals from higher structures. The anterior gray portion of the medulla contains neurons that are regulated by this complex integration of local signals and controls from above and send their impulses toward the muscles and the glands, through axon bundles that exit through the ventral nervous roots of the spinal cord.

Brainstem

The structure of the spinal cord continues within the skull (brainstem), where it keeps executing the same functions for the skin, the muscles and the glands of the face and the head, while it integrates further kinds of sensory information ‐ such as the ones coming from the vestibule, the organ of equilibrium, and from the ears, the tongue, the eyes.

However, in the brainstem the burden of elaborating and coordinating what is going on at lower levels of the medulla becomes more and more massive and complex.

In the nervous axis we therefore observe an input-output polarization, dorso-ventral ‐ from posterior (input) to anterior (output) ‐ and a hierarchical organization, climbing from the tail (missing in man...) to the head, the hierarchy being particularly relevant in the intra-cranial portion.

The impressive amount of information that passes through the inferior regions of the brainstem (bulb and pons) is partly dispatched to the cerebellum, that executes complex control elaborations and returns part of its results to the brainstem itself. A great fraction of motor behaviors is performed and coordinated almost completely at this level, with no need for any involvement of higher structures (brain); this is true in particular for instinctive motor schemes and learnt schemes that have become automatic (a fundamental role of cerebellum is precisely to learn and conduct automatic movements).

The information that passes through the brainstem and local elaboration gives rise to an intense activity of local neuronal groups, that diffusely project to various higher regions. Such activity is indispensable to maintain the cerebral cortex active, and permits maintaining alertness, attention and active behavior. If this input to the brain is missing (or is attenuated due to lesions, inflammation, pressure from internal bleeding or other causes), coma ensues.

The highest (and most anterior) region of the brainstem ‐ midbrain ‐ is the last tract that receives sensory information (visual information has a processing stage here). And the connections with the two cerebral hemispheres are inserted here. At this level, the coordination of all motor behaviors is complete: higher structures are not needed to perform complex tasks, such as breathing and swallowing, maintaining the upright position and executing the refined and coordinated sequence of movements needed to walk, at least on a plane ground and in the absence of obstacles. In addition, in the midbrain some important groups of neurons (nuclei) are located, that project to higher structures. One such nucleus, the substantia nigra, performs an essential activity of modulation of movements, and dysfunction of this structure results in Parkinson’s disease; another system of nuclei, in the ventral tegmental area (VTA), modulates in a coordinated way two distinct regions of the brain: one of these, the so-called limbic system, elaborates emotional experiences (part of this projection constitutes the so-called “reward pathway”, we shall talk about this later); the other target region, that is constituted by the most internal and anterior portions of the frontal cortex, is in charge of motivational control and thought and behavioral programming. The incorrect balance between these two control systems, originating from the midbrain, results in schizophrenia.