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Buzz of Life: One aspect of the interrelations among living entities. Researchers begin to understand the mechanisms governing the complex network interactions between plants and pollinators, such as hummingbirds, shown in this illustration from Ernst Haeckel's Kunstformen der Natur (1904).^[1]

The definition of life, the determination of the fundamental nature of living systems, and the explanation of life's origin and evolution, have engendered much thought, debate and research throughout history. At any given time in history, the prevailing perspective on life has depended on the extent of human knowledge at the time. This remains true.

Taking the perspective of early 21st century scientific knowledge, in this article we focus on describing the activity of entities we recognize as living. We focus on what essential activities living systems perform that enable their living — specifically, we focus on the fundamental processes of living, those that constitute the system that counts as living, the "common denominator that allows for the discrimination of the living from the non-living",^[2] as inferred from the study of Earth's living systems in the light of science.^[3]

We take as our theme the definition of Nobel prizewinning cellular/molecular biologist, Christian de Duve: "Life is what is common to all living things on Earth".^[4]  Those commonalities include the basic working unit of life, the biological cell, and the many molecular structures and processes cells have in common, including a boundary; the importation of energy and its application in performing cellular work; the exportation of more disorder than the order it generates within itself; metabolism; information processing and communication; self-organization and self-defense; adaptation; death; (re)production; and, cognition of self and the world outside itself.

What is Life?

Biologists use the word life in several of its many senses, to refer to:

• the biography of a living thing (— the life of a mountain gorilla — its life history), sometimes even after it/she/he has died (— the life of Albert Einstein);
• living things in the aggregate (— plant life);
• the relationships among living things (— the life of the forest);
• biology-related sciences (— she became a life scientist, specializing in plant physiology);
• intellectual or imaginative activity (— the life of the mind);
• all of the living things past and present (— evolution of life); and,
• the fundamental processes that characterize living things that distinguish them from non-living matter (— life as a unique self-fabricating material system).

Biologists use the latter sense of ‘life’ when asking "what is life?" and "what is the origin of life?"

Perhaps elsewhere in the universe we might find the same kinds of processes that characterize living things on Earth, or, foregoing geoanthropocentrism, we might find different kinds of processes generating entities that we might recognize as living. In this article, for life on Earth only can we make observations and draw a few provisional conclusions to the question, "what is life?".

Science can conceive that non-living matter could acquire naturally those processes that characterize living things. If living things developed from inanimate things, as science postulates, can we discover how that happened? We leave that question for an origin of life article. Here we focus on discovering the fundamental processes that uniquely characterize living things (on Earth), processes which origin-of-life researchers would need to know in order to target their search for the mechanisms that led to the transition of the non-living to the living.

The fundamental units and processes of living things: the sine qua non

Building blocks

On Earth, everything living teems with vibrant molecules of myriad types and sizes, too small for the naked human eye to see, but numerous enough to come into view as a flea or a giant sequoia tree (up to 4.5 million pounds of molecules).^[5][6] It inspires wonder that as particular collections of molecules, we humans can generate words shaped into metaphors that attempt to explain the very activity of living that enables that feeling of wonder. Notwithstanding the molecular foundation of living things, the atoms and molecules must first aggregate and organize as biological cells before anything living can emerge.

Science consider cells the units of life (life's atoms, so to speak). Living organisms can exist either as a single cell or as a community of interacting cells. In living nucleated cells, organic molecules exist in heterogeneous pools of colloidal aqueous solutions bounded by lipid-protein membranes (e.g., nuclei, mitochondria, endoplasmic reticulum (see Cell). Each pool can have a different composition with distinct properties (e.g., transmembrane electrical potential difference; density; viscosity; osmotic pressure; acidity; ionic strength) and different architectures. This heterogeneity provides the basis for the physiology that can cause electric fields, fluid shifts, energy transfers, and the transport of molecules into and out of the pools.

Although organic molecules contain a variety of atomic elements (especially hydrogen, oxygen, nitrogen, phosphorus, and sulfur), they always have a predominant structure of carbon atoms, typically linked as carbon-to-carbon bonds in diverse topologies. All cells share a common set of carbon-containing molecules - organic molecules, dissolved or dispersed in water as a common medium of housing and interaction — water comprises ~60-70% of the mature human organism. Those molecules include relatively small molecules, like amino acids, nucleotides, monosaccharides, and esters, and large macromolecules made up of sequences of smaller organic molecules. Organic macromolecules include proteins (sequences of amino acids), lipids, nucleic acids (sequences of nucleotides), polysaccharide (sequences of monosaccharides), and many other molecular genera.

The 'stuff' of life, then, is carbon-to-carbon chains, studded with other atomic elements, arranged in aqueous lagoons containing a variety of organic and inorganic molecules, interacting in accord with physico-chemical principles.

  —  Molecules

See related topics: Chemistry, Biochemistry, and Organic Chemistry

Why do carbon atoms play a central role in the chemistry of living things? The details of the physical chemistry of carbon reveal the principal reason. Carbon has four electrons in its outer shell, which has a capacity to hold eight electrons. The atom behaves as if it seeks four additional electrons to fill its outer shell to its capacity (see accompanying figure and caption). Metaphorically speaking, it usually achieves its goal by forming "covalent bonds" with other atoms, sharing electrons with other atoms also behaving as if they each sought to fill their outer shell. Thus, the physical chemistry of carbon enables it to bond with many other elements with unfilled outer shells. Those include hydrogen, which can share one electron with carbon to fill its [hydrogen's] outer shell, allowing carbon to covalently bond to four hydrogen atoms, as in methane (CH₄) [=natural gas]; oxygen, which can share two electrons with carbon to fill its [oxygen's] outer shell, allowing carbon to double-covalently bond with two oxygen atoms, as in carbon dioxide (CO₂, or O=C=O; and nitrogen, which can share three electrons with carbon to fill its [nitrogen's] outer shell, allowing carbon to triple-covalently bond with one nitrogen atom, as in hydrocyanic acid (HCN). Most importantly, carbon can share electrons with itself, allowing the formation of C-C bonds, including double bonds (C=C) and triple bonds. The avidity for carbon to bond to itself allows carbon atoms to join into long chains, sometimes with C-C side chains, or even closed rings of C-C bonds, with or without side chains. Rings and chains and branches of linked carbons can combine into almost any imaginable shape. The particular covalent bonding capacity of carbon thus enables it to combine with hydrogen, oxygen, nitrogen, and itself in multi-varied ways that generate small carbon-based molecules such as sugars, amino acids and nucleotides, which can join to become huge macromolecules with remarkable stability. The sequences of the varied subunits of such macromolecules, and the particular three dimensional shapes those sequences enable, give them the informational content required for self-assembling the dynamic organization of cells, for metabolic functioning, and for constructing copies of themselves.

(CC) Image: Anthony.Sebastian
Some of the ways carbon-carbon covalent bonds can configure.

The variety of carbon bonds vary in strength as well as in 3-D conformation. The simplest set of bonds that carbon can form is that of a tetrahedron, or pyramid, but the capacity of carbon for single, double and triple covalent bonding allows for many different geometries. Changing from one type of C-C bond to another type, as when a double bond is reduced to a single bond, will cause energy changes but without destroying the molecule. Such changes not only affect the molecule's energy state, but also affect the shape of the molecule and the particular side groups attached to it. One might say that the 'pulse of life' is represented at an atomic level.

(PD) Drawing: Anthony Sebastian
Atomic structure of the predominant isotope of a carbon atom: atomic number, Z=6; atomic mass = 12. Nucleus contains six protons (6p+) and six neutrons (6n). Electron configuration shown in rectangle. Outer shell (=valence shell) contains four electrons, has a capacity for eight electrons. The atom behaves as if it wants to fully fill its valence shell. With its valence shell fully occupied the atom achieves greatest stability as it has its least ability to react with other atoms. It usually achieves its valence shell octet of electrons by 'covalent' bonding, sharing electrons with other atoms, often with one or more other carbon atoms and one or more atoms of different elements also behaving as if they wanted to fill their own valence shells. See text.

The properties of carbon mean that organic macromolecules can contain huge 'banks' of information coded in their structure. Not only can each of the constituent molecules be huge, but several categories of chemicals, like nucleotides or amino acids, that contain several different species, can be ordered so that the possible combinations are effectively limitless. All of these molecules are involved in the molecular-interaction networks of cells.

Amongst those networks of molecular interactions are those that enable cells to import and transform energy and energy-rich matter from the environment and that ultimately enable cells to grow, survive and reproduce. Matter needs energy to vitalize it. D'Arcy Thompson, a pioneering biologist in the early 20th century, considered talking about molecules (or matter generally) only provides convenience in that enables us to abbreviate the nomenclature and description of the energies and their forces that give the molecular assembly living status.^[7]

Elsewhere in the universe, elements other than carbon and Earth-life's carbon-associated elements might give structure to living systems. Silicon, carbon's close columnar relative on the periodic table, also forms bond-chains with itself, forms covalent bonds with other elements, and supplies the basis for extraterrestrial living systems in fantasies by science fiction writers. Scientists conclude that silicon-silicon bonds do not stabilize under an Earth-like physico-chemical environment compatible with life as we know it.^[8]  Living systems, whether carbon-based or not, may not even require water to support the organization's chemistry.^[9]

For the possibility of extraterrestrial life based on inorganic matter see novel proposal of physicists Tsytovich et al.^[10][11] A mass of charged particles — like a swarm of bees — exhibiting features similar to Earth-type living systems

The possibility of non-molecular life, or life consisting of no matter at all (e.g., made up of energy fields), also interests science fiction writers. We science non-fiction writers consider energized molecules as the structural basis of living things on Earth.

  —  Cells

See Related Topics: Cell, Microbiology, Systems biology

In recognizing a living thing, biologists recognize it as a unity within an environment, yet apart from it — a compartment of a larger whole, structurally distinguishable though not functionally completely isolated from or closed to its surroundings. Every entity that biologists acknowledge as living — bacteria, trees, fish, chimpanzees — has a structurally compartmentalized building block, the biological cell. All cells extend themselves to (and include) an enclosing boundary that consists of a lipid-protein molecular membrane known as the cytoplasmic membrane, which structurally separates the interior of the cell from the external environment while allowing certain exchanges of energy and matter. The lipid molecules form the backbone of the cell membrane. ^[12]

Many organisms live as isolated cells, others as cooperative colonies of cells, and still others as complex multicellular systems that include diverse cell types, each specializing in different functions.^[13]  Nature has produced an enormous variety of cell types that span three vast ‘domains’ of living systems: Archaea, Bacteria, and Eukarya,^[14] yet cells in all three domains have many features in common. In particular, as described above, they have a surrounding membrane, a physical boundary that separates them from their environment. (Yet that generally accepted commonality may oversimplify: see^[15])  

The detailed composition of cell membranes differ among cell types, with differing protein types and auxiliary lipid species, enabling specific kinds of functional exchanges with the surroundings. Pores, receptor molecules and protective walls are often features of the cell surface, in both unicellular and multicellular entities.^[16]

Current evidence indicates that only pre-existing cells can ‘manufacture’ cells, so how did the first cell(s) arise? Examining what all cells have in common may provide insight to the origin of life. All extract energy from energy-rich molecules by simple oxidation reactions, and convert it into other, chemical forms of energy useful for cell function. The molecule ATP universally serves as the cell's main energy 'currency'. All cells inherit digitally stored information in the form of molecules of DNA, and with minor exceptions the DNA of all cells use the same universal genetic code to guide production of a myriad of distinct protein structures. Cells use those proteins to carry out diverse activities, including energy processing and conversion of carbon, nitrogen and phosphorous-containing materials into cellular structures. In the human genome, perhaps as few as 22,000 different protein-coding genes^[17] lead to the production of many times more distinct protein structures that make up the variety and quantity of protein molecules needed for the structures and functions of a cell. Numerous molecular mechanisms account for that quantitative gene-to-protein amplification.^[18]

Nature has produced a huge diversity of single-celled organisms and complex animals and plants. These can contain vast numbers of cells, each part of a specialized subpopulation (cell types) — in a mammal, the cells that make up bone differ in numerous structural and functional properties from those that make up muscle, and differ again from those that make up skin, for example. Humans contain approximately 200 different cell types as classified by microscopic anatomy.^[13] In multicellular organisms, cells combine to make organs, the functional and structural components of the single larger organism.

What makes a single celled organism 'alive', and does the answer apply also when we call a large complex multicellular animal or plant 'alive'? What exactly do we mean by 'living'? We turn to those considerations next.

The thermodynamics of 'living'

See also: Signed Article by John Whitfield: Survival of the Likeliest? — Using the laws of thermodynamics to explain natural selection — and life itself

Biologists have learned the importance of viewing living things from the perspective of thermodynamics — the science of interactions among energy, heat, work, and entropy (the degree of disorder of a system) and information (the degree of order of a system).^[20] These interactions define what a system can and cannot do when interconverting energy and work. For example, by the First Law of Thermodynamics, when a process converts one form of energy (e.g., light) to another (e.g., electricity), no net loss of energy and no net gain results, when the byproduct, heat, is taken into account.^[21] Once heat gets generated in an energy conversion, it becomes difficult to reverse the conversion. We can use sunlight to generate light back having a solar cell power a lightbulb, but do not get all the light back because some of the energy of sunshine converts to heat — i.e., it gets degraded to a lower 'quality' form of energy, less organized.

Scientists developed the laws of thermodynamics through experiment, debate, mathematical formulation and conceptual refinement; Albert Einstein believed that they stood as an edifice of physical theory that would never topple.

The Second Law of Thermodynamics has fundamental pertinence to the understanding of living systems:

(PD) Photo: Courtesy NASA/JPL-Caltech
Energy emitted by our sun provides the great bulk of the energy gradient that living systems on earth exploit, either directly or indirectly, to maintain a state far from the equilibrium state of randomness. The photograph shows a handle-shaped cloud of plasma (hot ions) erupting from the Sun.

• Heat flows spontaneously — i.e., without help from an external agency — from a region of higher temperature to one of lower temperature, and never spontaneously in the reverse direction. That also holds for other forms of energy, including electromagnetic and chemical energy: concentrations of energy disperse, down-flow, to lower energy levels, flowing, so to speak, "into the cool", and in the process, capable of doing work.^[22][23]
• When heat, as input to a system, causes it to perform work (e.g., as in a steam engine), it never converts the energy input entirely to work. Some of the heat always dissipates as ‘exhaust’, lower quality heat energy unusable by the system for further work. That also holds for other forms of energy doing work; some of the energy always turns into exhaust, typically heat. As empirical fact, conversion of energy to work in a system can never proceed at 100% efficiency.
• Consequences arise because work can produce order in a system, but always exports some of the energy input as a less organized form of energy, heat. Experiments reveal the balance sheet of order: the degree of order of a system (e.g., a living cell) and its surroundings together never increases when energy input causes the system to perform work; the 'net' order always decreases — disorder increases. Scientists have learned how to quantify the degree of disorder, and they refer to that quantity as entropy. Water vapor, with its molecules distributed nearly randomly, has a higher entropy (the molecules show a less ordered arrangement) than liquid water, with its molecules distributed less randomly, and a much higher entropy than ice, with its molecules distributed in a more ordered crystal-like array. Left to itself in an isolated system, ice tends to spontaneously melt and liquid water to evaporate. Order tends to disorder, with the Universe as a whole tending to exhaust itself into an ‘equilibrium’ state of randomness.

Water vapor in a glass jar, with its higher degree of disorder than it would have if it were liquid water in the jar, will, at room temperature, eventually settle at the bottom of the jar into a puddle of the more ordered liquid water. That decrease in disorder (entropy) of the jar-system can occur only because the water-vapor-filled jar-system is not an isolated system, closed off from energy exchange with its surroundings. The water-vapor-filled jar can export heat to the lower-temperature room as the water vapor condenses into liquid water, releasing the heat energy that maintained the water as vapor instead of liquid — an instance of energy flowing downhill, dissipating itself from a more to a less concentrated state. The exported heat, no longer a concentrated source of energy in the water vapor, becomes a less concentrated source of energy, distributed throughout the room, the jar-system's surroundings. Because experience has established that a system and its surroundings can statistically never spontaneously increase its degree of order — according to the Second Law of Thermodynamics, the room then becomes more, or minimally as much, disordered as the jar-system became more ordered. Thus, an open system can become more ordered spontaneously without conflict with the Second Law of Thermodynamics.

The above three expressions of the Second Law of Thermodynamics reflect the fact that energy and order spontaneously flow downhill — down a ‘gradient’— toward eliminating the gradient of energy.^[22] Upon eliminating the gradient by flowing downhill, no energy flows, all work production ceases, all order dissipates, and an equilibrium state of maximal disorder, entropy, ensues.

So, how do living entities, those manifestly energized organisms, come into existence — to develop from an embryonic state to one of more order and less entropy — and perpetuate their order? How do they thwart the Second Law of Thermodynamics?

They don’t: they only seem to do so. We saw, in the jar-filled water vapor example, that an 'open' system — one that can exchange energy with its surroundings — can order itself within the constraints of the Second Law of Thermodynamics. Living systems exploit the Universe’s gradients of energy and order. Like a steam engine, they 'import' energy and order, convert it to the work of building internal order in the form of a dynamic organization of constituent elements, which they fabricate themselves, and so fabricate a system of decreasing internal (within-system) entropy.^[24]  But, all along, they emit enough 'exhaust' to increase the disorder and entropy of their surroundings, so that the total entropy of the living system and its surroundings increases. Thereby the Second Law receives its due. The living system skims off a portion of the order flowing past it; it ingests order.

Biological cells qualify as non-equilibrium thermodynamic open systems. They ingest some of the energy that flows through them, and use it to keep away from the equilibrium state of randomness dictated by the Second Law. By exporting unusable energy as heat, they actually export more disorder (entropy) than they produce within themselves, thereby increasing the total entropy. They hasten the dissipation of the energy gradient they are in, as if nature's abhorrence of energy gradients 'favored' the origin, development and persistence of living systems to maximize the rate of entropy gain of the Universe as a whole.

Importantly, living things can store energy.

Recognition of the need for energy, as defined by the physicists, to enable life, has a long history.^[7] [25]

A living system always works far from the 'equilibrium' state of activity that would ensue if no energy could be imported, and energy from outside keeps the system far from equilibrium. Non-equilibrium thermodynamic open systems, including living things, can exhibit unexpectedly complex behaviors because of their far-from-equilibrium state, and one very remarkable behavior that can result is self-organization.^[26]

The sun (Sol) supplies much of the energy gradient that sources thermodynamic disequilibrium for living systems on earth. However, as Benner et al.^[27] point out,

Some biophysicists propose that the production of order by matter in an energy gradient, as in living things, tends to develop inevitably and proceed inexorably. They give two reasons: (1) the production of order through work, by exporting more than counterbalancing degrees of disorder, increases total entropy production (i.e., dissipates the energy gradient and renders the dissipated energy unusable) beyond that which would otherwise occur, and (2) energy sources dissipate their gradient to produce disorder at the fastest rate possible — to reach random thermal equilibrium as fast as they can. In other words, the physical principles governing energy gradient dissipation and energy degradation not only allows the development of living systems, but, in effect, tends to select for them — or urges their emergence — in particular, when no constraints are present disallowing their development (e.g., excess heat, poverty of appropriate resources. See additional argument in:^[28]

Thermodynamic principles thus contribute not only to answering the question “what is life?” but also to “why is there life?”.^[29] [30] Sir Arthur Eddington, the astronomer who first confirmed Albert Einstein's general theory of relativity, remarked:

Harold Morowitz and Eric Smith begin their essay on that perspective as follows:^[19]

Life is universally understood to require a source of free energy and mechanisms with which to harness it. Remarkably, the converse may also be true: the continuous generation of sources of free energy by abiotic processes [e.g., energy from radioactive decay deep in the Earth] may have forced life into existence as a means to alleviate the buildup of free energy stresses. This assertion — for which there is precedent in non-equilibrium statistical mechanics and growing empirical evidence from chemistry — would imply that life had to emerge on the earth, that at least the early steps would occur in the same way on any similar planet, and that we should be able to predict many of these steps from first principles of chemistry and physics together with an accurate understanding of geochemical conditions on the early earth. A deterministic emergence of life would reflect an essential continuity between physics, chemistry, and biology. It would show that a part of the order we recognize as living is thermodynamic order inherent in the geosphere, and that some aspects of Darwinian selection are expressions of the likely simpler statistical mechanics of physical and chemical self-organization.

See also commentary on Professors Morowitz and Smith's article.^[32]

Morowitz and Smith think that such order happens because it is a better 'lightning conductor' for discharging excess energy.^[32]

High energy (low entropy) cannot contain itself. When it has a channel to a lower energy (higher entropy) source, it discharges itself through the channel, causing patterns in space-time. Living systems provide such a channel for free energy from the sun and hydrothermal vents, because they actively consume energy and use it, in part to lower their own entropy, through growth and development and maintaining the living state. The system's surroundings receives the fruits of its labors, waste, translated as less usable energy than it would have without part of it already used up, and more entropy than without the lowering of entropy in the living organization because lowering entropy through incomplete conversion of energy to work generates entropy as waste. Living systems help relieve solar and vocanic pent-up energy, hastening its dissipation, justifying their cognomen as "dissipative structures".

We can, then, view a living system as a state of organizational activity maintained by importing, storing and transforming energy and matter — into the work of fabricating structures needed to sustain that state. They can only do so by producing waste and exporting it, and this lowers the ordered state of the environment. A living system maintains its organization at the expense of its external environment, leaving the environment more disordered than the gain in order of the living system — in keeping with the Second Law of Thermodynamics. Thus, from a thermodynamic perspective:

However, as physicist Philip Nelson writes: "The pleasure, the depth, the craft of our subject lie in the details of how living organisms work out the solution to their challenges within the framework of physical law."^[33] [Emphasis in original] To discuss those details would require invoking the facts and theories of biological physics, molecular and cell physiology, and systems biology, beyond the scope of this article if not the scope yet of those disciplines.

Metabolism

Can biology encompass living systems solely in terms of metabolism? Does'metabolism' capture all of the activities common to living systems and essential to their activity of living?

Some definitions may seem to synonymize metabolism and the activity of living:

....inclusive term for the chemical reactions by which the cells of an organism transform energy, maintain their identity, and reproduce. All life forms—from single-celled algae to mammals—are dependent on many hundreds of simultaneous and precisely regulated metabolic reactions to support them from conception through growth and maturity to the final stages of death. Each of these reactions is triggered, controlled, and terminated by specific cell enzymes or catalysts, and each reaction is coordinated with the numerous other reactions throughout the organism.^[34]

Chemical reactions do transform energy from one form to another, but they also capture energy, store it, use it to do work, waste it, produce more disorder than order from it — none of which the above description describes. Chemical reactions do help organisms maintain the identity of organisms, but they also help the organism generate its identity through self-assembly and self-organization. Can we subsume the interactions accounting for self-assembly and self-organization under the concept of 'metabolism'? Does 'metabolism' adequately describe the phenomenon of emergent behavior of living systems, however essential we recognize metabolism for the existence of a living system?

For the smallest living system, a cell, one might define metabolism as the activity constituting the aggregate interactions of all the energy-utilizing and energy-releasing chemical reactions occurring in the cell. By that definition metabolism provides at least a partial chart of the cell's activity.

Those considerations and questions do not imply that metabolism, appropriately characterized, does not qualify as an essential component in the activity of living as we know it from Earth life. All Earth's orgnisms 'metabolize.' Indeed, Harold Morowitz and Eric Smith^[19] recognize a “core metabolism” in all living systems and characterize it as follows:

....we know from analysis of entire genomes (citation to:^[35]) that the complete metabolic chart of autotrophs [organisms that synthesize their own food from inorganic materials and a source of free energy] has a universal core, based on a set of fewer than 500 small — less than 400 Dalton molecular weight–organic molecules. Within core metabolism, we recognize two major categories of function. Anabolism comprises the set of reactions that build organic compounds, while catabolism is the breaking down of organic compounds for energy or materials. Anabolism is essentially a reductive process, meaning that it consumes energy-rich electrons to create molecular bonds. It is possible for an organism to exist with anabolic reactions alone, if suitable electron donors [energy sources] are provided by its environment, and many major clades of anaerobic organisms that are thought to have very ancient lineage are autotrophs living on geochemical [energy] inputs (called chemo-autotrophs) whose metabolism is almost entirely anabolic (citation to:^[36])^[19]

Morowitiz and Smith describe the basic reductive (electron-donating, energy-storing) anabolic network as containing the carboxylic acids of the citric acid cycle and employing them to synthesize the biochemical precursors making up the cell. Non-autotrophs (heterotrophs, which feed on other organisms) use that network of carboxylic acids in an oxidizing (electron-removing) catabolic network (the Krebs cycle) to breakdown organic compounds to C02 and to free up energy. Morowitz and Smith point out that:

....when run in the reductive direction this cycle can duplicate its own members from abiotic CO2 and electrons, a property designated network autocatalysis. Thus the reductive citric-acid cycle appears, at the level of the biosynthetic network, to be a self-contained engine of synthesis for all biochemical precursors (citation to:^[37])^[19]

The core anabolic network, according to Morowitz and Smith, generates biological amino acids utilizing ammonia and electron donors (reducing agents, reductants), sugars, including ribose, from the citric acid cycle intermediate, pyruvate, cell membrane fatty acids from acetate, another intermediate of the cycle.

More elaborate pathways leading to the complex amino acids, nucleic acids, and cofactors, follow from these elementary steps in a dense and surprisingly simple web of reactions."^[19]

The core structurally-creative anabolic (energy-storing) network of autotrophs thus supplies the dynamical framework for energy to drive all living organization, as all living systems either are autotrophs or depend on the existence of autotrophs.

Evolutionary aspects of 'living'

Fires and storms have achieved status as living entities in human 'poetic/animistic' imagination. Although such non-living entities, such as tornadoes or the flames of candles, exist as non-equilibrium open thermodynamic systems, they lack essential qualities of Earth's living things. Tornadoes and candle flames cannot 'reproduce' themselves. Fire may spread and tornadoes may split, but the system that comprises each phenomenon does not self-replicate. Living systems have the capability of reproducing themselves.

When a living system reproduces itself, its offspring inherit its properties, but with variations introduced by random events (mutations). Some variations offer some of the offspring^[38] less opportunity to reproduce than others, and other offspring better opportunity, sometimes better even than their parents. Accordingly, new groups with different properties arise that may supplant older groups because of their greater reproductive fitness.^[39] Biologists call this "evolution by natural selection", and many, but not all,^{[40] [41] [42]} regard it as the most important way whereby living systems evolve over geological time.

Therefore, biologists recognize the ability to produce offspring that inherit some of its features, but with some variation, as an essential characteristic of living systems. They refer to it as descent with modification.^{[40] [42] [41]} Evolution by natural selection will occur if heritable variations produce offspring that differ in their reproductive fitness and if circumstances induce competition among conspecifics. The variations occur due to chance variations (e.g., mutations) in the inherited genetic database (genome) that the organism draws upon to the help it self-construct and self-maintain its organismic traits (phenotype), and also to various natural experiments (e.g., symbiogenesis) that lead to emergent genotype-phenotypes.^[40]

In all living systems, DNA primarily provides the database for the construction of their protein constituents. All living things descended with modification from an ancestral community of microorganisms with a partially shareable gene pool. (But see:^[43] To glimpse beyond that horizon, we will need to take heed of the findings of intense current research on early cellular evolution -- see Evolution of cells).

Viruses have few of these characteristics, but they do have a genotype and phenotype, making them subject to natural selection and evolution. Accordingly, descent with modification is not uniquely a characteristic of living systems. Beyond the scope of this article, we find descent with modification in memes and the artificial life of computer software, such as self-modifying computer viruses and programs created through genetic programming. Descent with modification has also been proposed to account for the evolution of the universe.^[44]

When it comes to the fundamental structures and processes of living, however, some biologists argue against the requirement for reproduction.^[45] NASA defines 'life' as a "chemical system capable of Darwinian evolution", without specification of reproduction per se (for discussion, see Benner et al.^[27]).

Adding to the thermodynamic perspective, we might say that:

Self-organization

In living systems, self-organization 'emerges' as a spontaneous manifestation of the interactions among the systems' components. In cells, self-organization emerges in part from so-called supramolecular (non-covalent) interactions of proteins-with-proteins and proteins with other molecules.^[46] [47] The proteins make their appearance through a genetic transcription-translation machinery, which itself represents a self-organized molecular machine that emerges in part from the non-covalent interactions of proteins with nucleic acids and other molecules.

Molecules interact by forming and breaking strong or weak covalent bonds, and also through weaker intermolecular interactions, like hydrogen bonding and Van der Waals forces. Those supramolecular interactions self-assemble aggregates of molecules (e.g., organelles, networks), giving them the properties that enable many biological processes.^[47][48] To quote Reinhout and Crego-Calama:^[49]

In chemistry, noncovalent interactions are now exploited for the synthesis in solution of large supramolecular aggregates. The aim of these syntheses is not only the creation of a particular structure, but also the introduction of specific chemical functions in these supramolecules.

And JM Lehn:^[50]

Starting with the investigation of the basis of molecular recognition, [supramolecular chemistry] has explored the implementation of molecular information in the programming of chemical systems towards self-organisation processes, that may occur either on the basis of design [by the chemist] or with selection of their components.

The qualifier that self-organization emerges in part from supramolecular interactions of proteins with proteins and other molecules reflects the need to invoke not only supramolecular self-assembly but also evolutionary mechanisms that produce and select genes that tend to optimize functional self-organization — in other words, adaptation. One must also invoke local real-time selective processes that confer stability and appropriate functionality to self-assembly, called homeostasis or adaptability. ^[51]

Professor of Microbiology, Franklin M. Harold, offers the following definition of self-organization:

...let me define self-organization as the emergence of supramolecular order from the interactions among numerous molecules that obey only local rules, without reference to an external template or global plan...The definition explicitly excludes order imposed by an external template, whether physical (as in a photocopier) or genetic (as in the specification of an amino acid sequence by a sequence of nucleotides)...The structure of the self-assembled complex is wholly specified by the structures of its parts and is therefore implicit in the genes that specify those parts: natural selection crafted those genes to specify parts that assemble into a functional complex.^[52]

Information resides in proteins and other molecules in virtue of their structure, and through them, information flows through cells, just as energy does, and determines their organizational nature.^[53]

One way to understand this self-organization is to view a living system as a 'computing device'. The inherited and acquired information base specifies components which arrange themselves in accord with their physico-chemical properties — i.e., they 'compute' the system in a complex chemical reaction. Yet that description under-characterizes the complexity of the system. In a multicellular organism, each cell retrieves only its own particular pieces of information from the total information base, and the selection varies with time. Each cell must perform specific computations to effect that dynamic activity. The behavior of the system's functional networks constitute those specific dynamic computations. The apparent circularity begat by adding that further characterization of the system as a 'computing device' exemplifies two-way nature of the 'computations' self-organizing the living system. With the tinkering and discovering comprising local trial-and-error and evolution’s handiwork, that 'circularity' carries out ('computes') integrative functions not explicitly encoded in the inherited and acquired information base of the system.^[54]

The molecular biologist Sidney Brenner^[55] expressed the 'computing device' metaphor this way:

...biological systems can be viewed as special computing devices. This view emerges from considerations of how information is stored in and retrieved from the genes. Genes can only specify the properties of the proteins they code for, and any integrative properties of the system must be 'computed' by their interactions. This provides a framework for analysis by simulation and sets practical bounds on what can be achieved by reductionist models.^[56]

The structure and behavior of self-organized systems need no behind-the-scene 'master controller', and no prepared blueprints that specify the structure and dynamics of the system. Instead, they emerge from interactions among the naturally generated and naturally selected components of a system, dictated by their physico-chemical properties, and dynamically modified by the emergent organization, which is itself modified by the environment. The single-celled zygote self-organizes into a multicellular living system as genetically encoded proteins interact, responding to changing influences from the changing environment generated by growing multicellularity — becoming a network of many cell-types working cooperatively.

That biological systems self-organize has led one prominent biologist to say they are products of a "blind watchmaker".^[57]

Self-organization tends to breed greater complexity of self-organization. One important aspect of self-organization in cells rests on the tendency for lipid molecules with polar (water-loving) and non-polar (water-shunning) ends to form bilayers in an aqueous solution, each unit of the bilayer with two lipid non-polar ends mutually attracted in the center and the polar ends surrounded by water. Protein molecules can span the bilayer membrane, or selectively straddle only one or the other side of the membrane and its aqueous surrounding, according to their specific amino-acid sequence and side-groups. Those lipid-protein membranes allow cells to communicate with other cells, either in free-living cellular communities or in multicellular organisms, and those communication activities self-organize by virtue of the properties of the cells, generated by natural experiments and selected for fitness by evolutionary mechanisms, and subject to downward effects by the systems' organization and environmental influences on the systems.

Self-organization occurs at all levels of living systems. For example, the dynamics of communities, such as the feeding relationships within communities of large mammals, also reflect self-organization. The animals and components of the ecosystem embedding them self-organize, resulting in "...unitary structures with coherent properties...[that] can operate in an integrated way, which allows for the acceptance of their changes on large time-scales as evolutionary."^[58]

Further elaborating the descriptions of living systems beyond the thermodynamic and evolutionary perspectives, we might say that:

Autonomous agents

(PD) Image: Courtesy drawingsofleonardo.org
Views of a Foetus in the Womb (c. 1510 - 1512) by Leonardo da Vinci. Although this near term fetus is a symbol of a new human life, the drawing is of a cadaver specimen.

Stuart Kauffman uses the concept of 'autonomous agents' to explain living systems.^[59] [60] He gives the hypothetical example of an enzyme that catalyzes the binding of two smaller sub-component molecules into a copy of itself — self-replication by auto-catalysis. The energy to produce the enzyme comes from a neighboring molecule, which, by breaking an energy-rich bond, serves as a 'motor' to produce excess enzyme. The self-replication stops after using all duplicates of the motor, so external energy — perhaps from light impinging on the system — must drive the repair of the broken chemical bond, re-establishing a supply of that energy-supplying molecule, thereby re-energizing the motor. A new cycle of auto-catalytic self-replication can then begin, given an influx of external energy and 'food' (sub-components of the auto-catalytic enzyme). As an essential feature, interactions among the components of a system have effects (technically 'allosteric' effects) that help organize and coordinate its processes, allowing the self-replication to proceed.^[59]

Kauffman conceives, then, of an autocatalytic molecule in a network of molecules that has cycles of self-replication driven by external energy and materials. Such a network is a 'molecular autonomous agent' because, given external energy and ample materials, the network perpetuates its existence;. The network is autonomous because it is not controlled by outside forces even though it depends on outside energy and materials. The 'agent' is the system doing work autonomously; in this case, the work of self-replication. (That's what 'agents' do; they do work.) In this example, the agent survives by ‘eating’ outside materials and energy. Work gets done because the system remains far-from-equilibrium: as energy flows through the system, the system does its work, and in so doing dissipates the energy gradient, but it temporarily constrains the rate of dissipation by storing energy in its internal organization. The agent continues to "live" only while that far-from-equilibrium state exists, and it can be starved to 'death' by stopping the matter and energy from flowing through the system. Kauffman argues that cells, and indeed all living systems, qualify as autonomous agents, constructed from molecular autonomous agents.^[59]

Autonomous agents also interest scientists in the fields of artificial intelligence and artificial life. One careful description of autonomous agents from some members of that group adds further insight to this view of living systems:

An autonomous agent is a system situated within and a part of an environment that senses that environment and acts on it, over time, in pursuit of its own agenda and so as to effect what it senses in the future. It has the properties of reactivity (timely response to environmental changes; autonomy (controls its own actions); goal-orientation (pursues its own agenda); continuous processing. Some autonomous agents may also have the properties of communicability (with other agents); adaptability (based on previous experience); unscripted flexibility.^[61]

For Kauffman, the property of pursuing its own agenda includes contributing to its own survival and reproduction: "...an autonomous agent is something that can both reproduce itself and do at least one thermodynamic work cycle. It turns out that this is true of all free-living cells, excepting weird special cases. They all do work cycles, just like the bacterium spinning its flagellum as it swims up the glucose gradient. The cells in your body are busy doing work cycles all the time."^[62] There is only one escape from work, and that is death.

If the descriptions of living systems from thermodynamic, evolutionary, self-organizational and autonomous agent perspectives are considered, we might add that:

Networks

(CC) Drawing: David K. Gifford, et al
The modular organization of a cellular network. Yeast Transcriptional Regulatory Modules. Nodes represent modules, and boxes around the modules represent module groups. Directed edges represent regulatory relationship. The functional categories of the modules are color-coded.^[63]

The science of networks^[64] provides another useful perspective on living things. Networks ‘re-present’ a system as 'nodes’ and ‘interactions’ among the nodes (also referred to as ‘edges’ or ‘arrows’ or ‘links’). For example, in a spoken sentence, words and phrases make up the nodes, and the interconnections of syntax (subject-to-predicate, preposition-to-object of preposition, etc.) make up the links. Intracellular molecular networks represent specific functions in the cell; molecules make up the nodes, and their interactions with other nodes make up the edges or arrows. Some networks accept inputs of one kind and return outputs of a different kind.

One finds networks everywhere in biology, from intracellular signaling pathways, to intraspecies networks, to ecosystems. Humans deliberately construct social networks of individuals working (more or less) to a common purpose, such as the U.S. Congress; they also construct networks of electronic parts to produce, for example, mobile phones; and networks of sentences and paragraphs to express messages, including this very article. Researchers view the World Wide Web as a network, and study its characteristics and dynamics.^[64] [65]

According to Alon, "The cell can be viewed as an overlay of at least three types of networks, which describes protein-protein, protein-DNA, and protein-metabolite interactions."^[66] Alon notes that cellular networks are like many human engineered networks in that they show 'modularity', 'robustness', and 'motifs':

• Modules comprise subnetworks with specific functions differing from those of other modules, and which typically but not invariably connect with other modules, often only at one input node and one output node. An individual module achieves its status as a distinct entity not only by its functional specificity but also by spatial specificity (e.g., ribosomes) or by chemical specificity (e.g., signal transduction networks). Modularity helps to facilitate real-time system adaptability to environmental change, as the organization of modules in the system contributes to the emergent properties of the system.^[67]  It also facilitates evolutionary adaption, as, to select an adaptation, evolution may need tinker with just a few modules rather than with the whole system. Evolution can sometimes 'exapt' existing modules for new functions that contribute to reproductive fitness. For example, Darwin surmised that the swim bladder of skeletally heavy fish evolved as an adaptation for control of buoyancy but was exapted as a respiratory organ in certain fish and in land vertebrates. ^[39] [68]
• Robustness describes how a network is able to maintain its functionality despite environmental perturbations that affect the components. Robustness also reduces the range of network types that researchers must consider, because only certain types of networks are robust.^[69]
• Network motifs offer economy of network design, as the same circuit can have many different uses in cellular regulation, as in the case of autoregulatory circuits and feedforward loops. Nature selects motifs in part for their ability to make networks robust, so systems use motifs that work well over and over again in many different networks.^[70] In several well-studied biological networks, the abundance of network motifs — small subnetworks — correlates with the degree of robustness.^[71] Networks, like those in cells and those in neural networks in the brain,^[72] use motifs as basic building blocks, like multicellular organisms use cells as basic building blocks. Motifs offer biologists a level of simplicity of biological functionality for their efforts to model the dynamics of organized hierarchies of networks.^[70]

The view of the cell as an overlay of mathematically-definable dynamic networks can reveal how a living system can exist as an improbable, intricate, self-orchestrated dance of molecules.^[73] The 'overlay of networks' view also suggests how the concept of self-organized networks can extend to all higher levels of living systems.

Further elaborating the descriptions of living systems beyond the thermodynamic, evolutionary, self-organizational and autonomous agent perspectives we might add that:

Information processing

Bioscientists study biological systems for many different reasons, hence biology has many subdisciplines (see Biology and List of biology topics). But in every subdiscipline, bioscientists study biological systems for the proximate reason of gaining information about the system to satisfy their however-motivated curiosity and to apply that information to human agendas (e.g., to prevent disease, to develop treatments, to enhance health and longevity, to conserve the environment, etc.). Those realities attest that biological systems harbor information, at least as people usually understand the term. To appreciate how that perspective can contribute to understanding living systems, the following questions need answers:

• What do we mean by information?
• How does information apply to biological systems?
• How does information emerge in biological systems?
• How do the answers to those questions add to explaining living systems?

(PD) Drawing: U.S. Department of Energy
Information processing from DNA to a living system. Genes, composed of DNA, contain the information used by other cellular components to create proteins. A cell is tightly packed with tens of thousands of proteins and other molecules, often working as multi-molecular 'machines' to perform essential cellular activities.

A drinking glass falls onto the sidewalk, it falls apart into a random collection of bits of glass. Notice it doesn’t regroup into the drinking glass — you could watch it for a lifetime. Our experience shows us that the drinking glass is more improbable than the glass smithereens. The more improbable the arrangements, the more in-formation a collection of parts has received and therefore contains. An observer will conclude that something has happened to form the parts into a more improbable state — an in-formation has occurred, and that the collection of parts contains that in-formation. By that reasoning, biological systems contain in-formation: something has happened to 'form' the parts into an improbable state.^[74]

An ordered desktop soon becomes disordered. The ordered desktop has message value, or 'information', in that something must have happened to give it form. The more unlikely the arrangement of the parts, the more information it contains. Biological systems have information content in that they are unlikely (non-random) arrangements of parts, non-random collections of interactions of parts, and non-random collections of functional activities.

The above-discussed thermodynamic and autonomous agent perspectives viewed cells as interposed between a higher-to-lower degrees of usable (free) energy — embedded in downward sloping free energy gradient. The flow of energy through the cell fuels it, enabling it to perform the work that leads it to gain form, or order, or organization, and to gain functionalities, which raises its information content.^[75]

Thus a living system emerges as an information processing system. It can receive information from energy^[76] and energy-rich materials in its environment, which fuels and supplies the self-organizing machinery that builds and sustains an information-rich organization; it can generate new information inside itself, as in embryonic development; and it can transmit information within and outside itself, as in transcription regulation and exporting pheromones. From its parent(s), it inherits information (genetic) that provides a database to help it realize its developmental potential — including information critical for its self-reproduction, though it also inherits information in non-genetic forms (epigenetic, behavioral, symbolic) that contribute to its development.^{[41] [77] [42]}

Physiologist and Director of the Laboratory of Cell Communication at the Marine Biological Laboratory, Woods Hole, Massachusetts, Werner R. Loewenstein^[53] emphasizes the reciprocal relationship between changes in information and changes in entropy: “…we may regard the two entities as related by a simple conservation law: the sum of (macroscopic) information change and entropy change in a given system is zero. This is the law which every system in the universe…must obey.” He elaborates:

"Living beings continuously lose information and would sink to thermodynamic equilibrium just as surely as nonliving systems do. There is only one way to keep a system from sinking to equilibrium: to infuse new information…[T]o maintain its high order, an organism must continuously pump in information. Now, this is precisely what the protein demons do inside an organism. They take information from the environment and funnel it into the organism. By virtue of the conservation law, this means that the environment must undergo an equivalent increase in thermodynamic entropy; for every bit of information the organism gains, the entropy in the demon's environment must rise by a certain amount. There is thus a trade-off here, an information-for-entropy barter; and it is this curious trade which the protein demons ply. Indeed, they know it from the ground up and have honed it to perfection. Bartering nonstop, they draw in huge information amounts, and so manage to maintain the organism above equilibrium and locally to turn the thermodynamic arrow around."

Paul Nurse, cell biologist and president of Rockefeller University, prompts for greater focus on discovering just "how living systems gather, process store and use information" and how higher level biological phenomena emerge from such information self-management.^[78] One can envision logic circuits as proximal products of the molecular interactions occurring in a living cell, and envision ultimately the operation of selective forces in the development of those logic circuits. To understand living systems requires understanding living information processing.

Combined with other perspectives, viewing living systems as information processors, as inheritors, receivers, generators and transmitters of information, and as reproducers of inherited information, enables one to see living systems and their interactions with other living systems as a vast, complex, emergent, naturally-selected, self-sustaining, evolving communications network. Recently, on the timescale of evolving living systems, that evolving communications network emerged as the human brain, capable of communicating with itself and other humans using networks of symbols.^[79] That led to the emergence of cultural evolution, a whole new domain of self-reproducing entities ('culturgens', 'memes') and a whole new domain of descent with modification. That in turn led to the emergence of other vast communications network: books, wikis, and other technologies of information generation and exchange.

We might now consider another closely related perspective, a ‘cognitive’ perspective.^[80] Given that networks resist common perturbations (e.g., by their robustness, and by ‘homeostasis’), one might think of them as containing a representation of themselves and of their environment, and of how they might vary. As networks self-organize through interactions among proteins, any network-like 'representation’ of of the living system embedding it, and its environment, must derive from the information that determines those proteins. The genetic information comprises a molecular code, and the process that transforms that information into proteins describes an algorithm — the transcription-translation algorithm, including its regulatory circuits. Inasmuch as those algorithms evolved through natural experiment and selection, one can view evolution as selecting for cognitive functionality in the genome — the ability to ‘represent’ the cell’s state and environment and, more generally, to remember and anticipate.

Genetic information has the form of a digital code, one whose execution jump-starts self-organizing cellular processes, including the processes that lead to self-organization of networks that regulate execution of the genetic digital code — the gene regulatory networks. A separate digital code also has a central role in the operation of those gene regulatory networks: the code adjacent to a gene determines which transcription regulating factors can bind there, and thereby controls gene activity. In other words, a digital code, separate from the code that specifies the proteins of the gene regulatory networks, gives specificity to the behavior of those networks and to their regulation of the execution of the genetic digital code.^[81] Eventually, digital codes surrender to decipherment, offering the hope that we might someday read the message they contain and find ways to edit it.

Further elaborating beyond the thermodynamic, evolutionary, self-organizational, autonomous agent and network perspectives we might add that:

Living systems as self-fabricating autonomous homeostatic cognitive machines

In this section we consider living systems, as distinct from non-living systems, from the perspective of the concept of ‘autopoiesis’ — autonomous self-fabrication — introduced in the 1970s by Humberto Maturana (b. 1928) and Francesco Varela (1946-2001),^[82] though first enunciated, as pointed out in 2007 by J-H S. Hofmeyr,^[83] by the philosopher Immanuel Kant (1724–1804),^[84] and adumbrated by twentieth century biologists before Maturana and Varela.^[85].

Microbiologist Harold Frank elaborates on Kant's view:

In a machine, [the German philosopher, Immanuel] Kant said, the parts exist for each other but not by each other; they work together to accomplish the machine's purpose, but their operation has nothing to do with building the machine. It is quite otherwise with organisms, whose parts not only work together but also produce the organism and all its parts. Each part is at once cause and effect, a means and an end. In consequence, while a machine implies a machine maker, an organism is a self-organizing entity. Unlike machines, which reflect their maker's intentions, organisms are “natural purposes.” Kant's vision was eminently sensible and remains true, but even he was stymied by the next stage: How can we ever discover the cause of that purposeful organization that is the hallmark of organisms?^[86]

Any entity we recognize as living we recognize also as a ‘system’, an assemblage of components, interrelated structurally, interacting in a coordinated, dynamic, hierarchical way such as to self-construct an autonomously working organization characterizable as a ‘whole’ or ‘operational unit’ in virtue of a boundary selectively separating it from its environment — a kind of universe unto itself. We can hold that view of living systems regardless of the nature of the components that self-construct it, but on Earth we recognize those components as matter in the form of atoms and molecules, importing, converting, storing, releasing free energy, and actuated by it.

The precise description of the organization of living things differs widely among species. Think of an ant and an anteater. We can, however, specify characteristics of the ‘kind’ of organization that all species share here on Earth. For one thing, we can say a living system’s complexity exceeds current human cognitive ability to comprehend it, even with the aid of a powerful computer exo-cortexes. Arguably, in the future that characteristic of the organization in living things may prove non-constitutive.

We can say also that the organizational state of living systems resembles that of a man-made machine, like a super-jet airplane or a super-computer, though not made by man and not obviously having a purpose except to perpetuate its activity of living. We can think of a living system as a different ‘kind’ of machine than man-made machines. We can see that living machines exhibit a natural, or non-contrived ability to keep many of its internal variables constant, or within narrow bounds — it qualifies as a homeostasis machine.

A living system’s homeostatic ability plays a critical role in defining its uniqueness, as it enables it to homeostatically regulate the most important variable required for its continued living: an organization, whatever its description, that perpetuates its existence as a living system. Through the activity of its organization, the living system produces those components that provide the structural basis for the self-construction of its state as an autonomously working organization. If a living system cannot self-maintain its organization, it cannot produce the structure whose self-constructed coordinated interactions enable it to remain a living machine.

Autopoiesis co-founder Francisco Varela summarizes thusly:

Autopoiesis attempts to define the uniqueness of the emergence that produces life in its fundamental cellular form. It's specific to the cellular level. There's a circular or network process that engenders a paradox: a self-organizing network of biochemical reactions produces molecules, which do something specific and unique: they create a boundary, a membrane, which constrains the network that has produced the constituents of the membrane. This is a logical bootstrap, a loop: a network produces entities that create a boundary, which constrains the network that produced the boundary. This bootstrap is precisely what's unique about cells. A self-distinguishing entity exists when the bootstrap is completed. This entity has produced its own boundary. It doesn't require an external agent to notice it, or to say, "I'm here." It is, by itself, a self- distinction. It bootstraps itself out of a soup of chemistry and physics.” ^[87]

We can view a living system then as:

• A self-constructed machine organized as a network of interactions that fabricate, cyclically, the components whose self-organized interactions self-construct the system’s self-perpetuating network of interactions.
• A self-constructed machine organized as a network of interactions that can respond to perturbations either by self-correction of its disturbed organization (homeostasis), or by reorganizing itself into a different self-perpetuating network of interactions (adaptability; reproduction).

We can encapsulate that view of living systems preliminarily as ‘self-constructed self-perpetuating homeostatic machines’. Maturana and Varela^[82] introduced the term ‘autopoiesis’ and ‘autopoietic organization’ to encapsulate that view of living machines as self-constructed self-perpetuating homeostatic machines as we have characterized them.  Bitbol and Luisi expressed the definition of autopoiesis as follows:^[88]

The theory of autopoiesis...captures the essence of cellular life by recognizing that life is a cyclic process that produces the components that in turn self-organize in the process itself, and all within a boundary of its own making.

That view of a living system reveals a special property of homeostasis in living machines: adaptability. A human, to take an example mammal, self-perpetuates a life-sustaining organization despite enormous perturbations of its organization during embryonic and fetal ‘development’. It does it by self-reorganizing — the homeostatic property of adaptability. If we think a fetus or a child an immature adult, we must think of adults as aged fetuses or children. As one individual or identity, fetus and adult represent a single self-constructing self-perpetuating homeostatically adaptable machine.

Ontogeny highlights the living system’s unique property of homeostasis in targeting with highest priority the maintenance of an organization that produces components that self-organize a network of interactions that perpetuates that organization — including its networks of interactions that retain its homeostatic property of adaptability. Homeostatic reorganization goes on continuously. The living machine maintains networks of interactions that define it as a self-constructing self-sustaining machine.

The self-constructed self-perpetuating homeostatic machine also produces its own boundary, as without that it could not maintain its organization against all the chaos outside.

A man-made, non-living machine yields products other than itself, products for human use. A living machine yields itself as its product, a product in continuous production, no matter how much it must modify itself in the process.

Therein defines the living machine’s autonomy —- it works in its own behalf to construct and sustain itself. So central to a living machine's uniqueness, its homeostatic organizational ability to produce components whose interactions self-organize a self-perpetuating organization, that, before accumulated perturbations of its organizat