Life

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This editable Main Article has an approved citable version (see its Citable Version subpage). While we have done conscientious work, we cannot guarantee that this Main Article, or its citable version, is wholly free of mistakes. By helping to improve this editable Main Article, you will help the process of generating a new, improved citable version.

[edit intro]

This article is about the definition of Life. For other uses of the term Life, please see Life (disambiguation).

Bear with me, 0 mystery of existence, as I pluck the occasional thread from your train.

— Wislawa Szymborska, from her poem, "Under One Small Star"

* * *

(PD) Image: Ernst Haeckel
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]

Throughout history, we humans devoted much thought, speculation, debate, and research in an attempt to explain the fundamental nature of living systems and to explain their origin and biodiversity -- in short, in an attempt to define life.

The typical form of the question asked: "What Is Life?"

At any given time in history, the prevailing answers to that perennial question depended on the prevailing extent of human knowledge, and to the cultural interpretations given that knowledge, including those arising from belief systems based on myth and religion-inspired faith. At this writing, in mid-second decade of the 21st century, that still remains the case.[2]

Scientist, historian, and philosopher, Evelyn Fox Keller speaks to the issue of historical context in making sense of life:

> [W]hat is to count as knowledge? As explanation? As theory? Philosophers of science have traditionally tended to approach such questions in the abstract, as if they could be answered independently of historical or disciplinary context.

>  My own experience, as both a scientist and an historian...persuades me that answers to such questions are not given but contingent; not universal but rather matters of local and historically specific, disciplinary culture...once I was alerted to the problem, other variations in epistemological culture became evident as well...These reflect differences in questions, in available technology, in resources, and in cognitive, practical, and psychological needs.

>  In other words, my interest here is not in what should count as an explanation in science but on what does count. And for this, one must look to the explanatory conventions operative at particular times and in particular areas of scientific research.[2]

In keeping with Keller's thesis, we treat this article from the perspective of early 21st century scientific knowledge, including emphasis on the explanatory conventions of this particular time. In particular, we focus this article on what scientific research has revealed of the common activities that living systems perform to enable their continuing living. Specifically, we focus on the fundamental processes of the activity of living, those that constitute a system that counts as a living system, those processes qualifying as the "common denominator[s] that allows for the discrimination of the living from the non-living",[3] as inferred from the study of Earth's living systems in the light of modern science.

## To make a start[edit]

## Contents

* 1 To make a start
* 2 What is Life?
* 3 The fundamental units and processes of living things
* 3.1 Building blocks
* 3.2 · Biological cells, in profuse variety of types
* 3.2.1 — Molecules
* 3.2.2 — Cells
* 3.3 The thermodynamics of 'living'
* 3.4 Metabolism
* 3.5 Evolutionary aspects of 'living'
* 3.6 Self-organization
* 3.7 Autonomous agents
* 3.8 Networks
* 3.9 Information processing
* 3.10 Autopoiesis
* 3.11 A hierarchy of emergent systems
* 3.12 Emergence
* 3.13 Spectrum of emergence in biology
* 4 Fundamental underpinning of living systems
* 4.1 Different scientific perspectives
* 4.2 Synthesis of perspectives
* 4.2.1 Life abstracted
* 4.2.1.1 A non-Earth-centric non-matter-centric perspective
* 4.2.1.2 An Earth-centric matter-centric perspective
* 5 Supplementary text
* 6 References
* 6.1 Citations and notes

We take as our theme the definition of life given by Nobel prizewinning cellular/molecular biologist Christian De Duve: "Life is what is common to all living beings".[4] Those commonalities, expanded and discussed in detail below, include:

* basic inorganic and organic chemical constituents;
* a fundamental working unit and building block, biological cells -- the 'atoms' of living systems;
* a hierarchy of networks of molecular and supramolecular structures, interrelationships and interactions;
* a boundary that both separates a cell from its external environment and enables it to exchange matter, energy, and information with that environment to maintain the activities of living;
* importation of energy, and its application in performing cellular work;
* exportation of more disorder than the order generated within itself;
* a core metabolism;
* within-cell and between-cells communication and computational information processing;
* self-assembly, self-organization, self-defense, and self-repair;
* resistance to perturbations of vital functions and mechanisms to restore deviations to normal (homeostasis);
* allostasis, physiological mechanisms that enable the system to adjust beneficially to diverse stressors through adaptive changes in physiology
* real-time and cross-generation adaptation, including learning;
* emergent behavior;
* self-reproduction;
* cognition of self and the world outside the self;
* death.

Life is one. This fact, implicitly recognized by the use of a single word to encompass objects as different as trees, mushrooms, fish, and humans, has now been established beyond doubt. Each advance in the resolving power of our tools, from the hesitant beginnings of microscopy little more than three centuries ago to the incisive techniques of molecular biology, has further strengthened the view that all extant living organisms are constructed of the same materials, function according to the same principles, and, indeed, are actually related. All are descendants of a single ancestral form of life.
--Christian De Duve, Vital Dust

In stating that Life is what is common to all living beings, De Duve explains:

> This answer is not a tautology, as it allows many attributes to be excluded from the definition of life...What remains is what we humans have in common with the colibacilli in our gut. It is still a lot...We and colibacilli, together with all other living beings, are made of cells, which are constructed with the same substances. We build our constituents by the same mechanisms. We depend on the same processes to extract energy from the environment and convert it into useful work. Most telling of all, we use the same genetic language, obey the same code. There are differences, of course. Otherwise, we would all be identical. But the basic blueprint is the same. There is only one life...We and colibacilli are distant cousins; very distant, but indubitably related.[4]

## What is Life?[edit]

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

No one can deny the extraordinary advances that have been made over the course of this past century in our understanding of vital processes…Yet I would argue that, despite such unquestionable success, biology is scarcely any closer to a unified understanding (or theory) of the nature of life today than it was a hundred years ago. The models, metaphors, and machines that have contributed so much to our understanding provide neither unity nor completeness. They work to answer some questions while avoiding (even obscuring) others; they satisfy certain needs while failing to address others; in short, they leave the project of "making sense of life" with an essentially-and perhaps necessarily-mosaic structure.

--Evelyn Fox Keller[2]

* the biography or lifeway 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;
* a way of living -- she led the life of an artist;
* living things in the aggregate -- plant life, marine 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 shared fundamental processes that characterize living things and 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?"

Science can conceive that non-living matter might 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.[5] Here we focus on discovering the shared fundamental processes that uniquely characterize living things (on Earth), those elementary processes that 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.

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 answers to the question, "what is life?". Some doubt even the provisionality of those answers (see textbox this section).

## The fundamental units and processes of living things[edit]

In other words, sine qua non of the activity of living.

### Building blocks[edit]

The task of supramolecular chemistry is to explore and develop systems which are programmed to form selective self-assembling, self-recognizing, and finally self-learning entities.

-- Elina Ventola

Whether matter ultimately has substance/materiality or not,[6] biologists usually consider living systems as material structures made up of abundant replicates of numerous different types of atoms, giving rise, by means of a wide variety of types of chemical bonds, to small and large molecules and supramolecular complexes, spatiotemporally dynamically interacting in self-organizing networks in a matrix of the chemical compound, water. On Earth, in a water-based medium embedding and permeating the interstices of living systems, every living system teems with thermally sustained vibrating and jostling molecules of myriad types and sizes, too small for the naked human eye to see, but numerous enough to manifest themselves, collectively, as a flea or a giant sequoia tree, the latter of which may consist of up to 4.5 million pounds of molecules.[7] [8]

It inspires wonder that as particular collections of water embedded matter, powered by external energy to perform work to enable self-organized autonomy, we humans can electrically generate words shaped in metaphors that attempt to explain the very activity of living that enables that feeling of wonder, that render the human living system aware of itself as living, and as a living system.

###  · Biological cells, in profuse variety of types[edit]

Notwithstanding the atomic and molecular foundation of living things, the atoms and molecules must first self-assemble and self-organize as biological cells before anything living can emerge.

Science considers cells the units of life (life's atoms, so to speak). Living organisms can exist either as single cells (e.g., amoebae, paramecia, bacteria) or as communities of coherently and dynamically interacting cells (e.g., colonies of prokaryotes, integrated multicellular organisms like plants, animals). In living cells, organic molecules exist in heterogeneous pools of homogeneous and colloidal aqueous solutions bounded by lipid-protein-carbohydrate membranes (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; redox state) and different orderly arrangements of parts. That heterogeneity, self-organized, provides the basis for the physiology that can cause electric fields, fluid shifts, energy transfers, within-cell and between-cell communication, 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 manifold 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 typically comprising 60% or more of a cell, organ, and 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.

By mass, a typical mammalian cells consists of about 70% water, 18% protein, 5% lipids, 2% polysaccharides, 1% DNA and RNA, and 4% diverse chemicals, organic and inorganic.[9]

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

####  -- Molecules[edit]

From Molecule to Metaphor
--Jerome A. Feldman

See related topics: Chemistry, Biochemistry, and Organic Chemistry

Why do carbon atoms play a central role in the chemistry of living things? The answer emerges from the details of the physical chemistry of carbon. 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 carbon-bonding elements 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. 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.

(PD) Drawing: Anthony Sebastian

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:

> Matter as such produces nothing, changes nothing, does nothing; and however convenient it may afterwards be to abbreviate our nomenclature and our descriptions, we must most carefully realise in the outset that the spermatozoon, the nucleus, the chromosomes or the germ-plasma can never act as matter alone, but only as seats of energy and as centres of force. [10]

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.[11]

Living systems, whether carbon-based or not, may not even require water to support the organization's chemistry.[12]

Some physicists and science writers propose that extraterrestrial life may develop based on inorganic matter:[13]

> Complex plasmas [a state of matter common in outer space consisting of a mass of charged particles] may naturally self-organize themselves into stable interacting helical structures that exhibit features normally attributed to organic living matter. The self-organization is based on non-trivial physical mechanisms of plasma interactions involving over-screening of plasma polarization. As a result, each helical string composed of solid microparticles is topologically and dynamically controlled by plasma fluxes leading to particle charging and over-screening, the latter providing attraction even among helical strings of the same charge sign. These interacting complex structures exhibit thermodynamic and evolutionary features thought to be peculiar only to living matter such as bifurcations that serve as `memory marks', self-duplication, metabolic rates in a thermodynamically open system, and non-Hamiltonian dynamics. We examine the salient features of this new complex `state of soft matter' in light of the autonomy, evolution, progenity and autopoiesis principles used to define life. It is concluded that complex self-organized plasma structures exhibit all the necessary properties to qualify them as candidates for inorganic living matter that may exist in space provided certain conditions allow them to evolve naturally.

####  -- Cells[edit]

Omnis cellula e cellula
--Rudolf Carl Virchow (1821–1902)

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. A structurally compartmentalized building block, the biological cell, underpins very entity that biologists acknowledge as living -- bacteria, trees, fish, chimpanzees. 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. Lipid molecules form the backbone of the cell membrane, a cell-enclosing lipid raft with proteins of different types floating in it, floating often with 'tentacles' sticking out of lipid external boundary and into the cell interior, serving as specialized links for transfer of information into and out of the cell.[14]

(PD) Drawing: National Library of Medicine
Eukaryotes and prokaryotes. This figure illustrates a typical human cell (eukaryote) and a typical bacterium (prokaryote). The drawing on the left highlights the internal structures of eukaryotic cells, including the nucleus (light blue), the nucleolus (intermediate blue), mitochondria (orange), and ribosomes (dark blue). The drawing on the right demonstrates how bacterial DNA is housed in a structure called the nucleoid (very light blue), as well as other structures normally found in a prokaryotic cell, including the cell membrane (black), the cell wall (intermediate blue), the capsule (orange), ribosomes (dark blue), and a flagellum (also black).

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.[15] Nature has produced an enormous variety of cell types that span three vast ‘domains’ of living systems: Archaea, Bacteria, and Eukarya,[16] 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[17])

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.[18]

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 cells. 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 begin life with a part of its parent's cytoplasm and its organelles, and inherit digitally stored information in the form of molecules of DNA. 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[19] 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.[20]

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.[15] 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'[edit]

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.

--Harold Morowitz and Eric Smith[21]

We propose that the only absolute requirements [for life] are a thermodynamic disequilibrium and temperatures consistent with chemical bonding.

--S. A. Benner et al.[22]
Organisms do not maintain their complexity, and become more complex, in a vacuum. Their high organization and low entropy is made up for by pollution, heat, and entropic export to their surroundings.

--Eric D. Schneider and Dorion Sagan
The second law is the Greatest Good and the Biggest Bad to us...You can't get any better for good -- that living is possible due to the second law. And you can't get much worse for bad -- that death is always possible too, due to the second law.

--Frank L. Lambert[23]

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).[24] 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.[25] 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 light-bulb, 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.[26] [27]
* 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 it 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.[26] 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.[28] 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.

Biologist Alexei Kurakin remarks that:

> ...the apparent conflict between the second law of thermodynamics and biological evolution exists only if one assumes that the energy/matter comprising the Universe is near equilibrium and that it evolves toward an equilibrium state via disorganization and disordering, obeying the laws of equilibrium thermodynamics. The conflict disappears, however, if we postulate that the energy/matter making up the Universe is far from equilibrium, that it exists as an evolving flow, and that the energy/matter flowing through and comprising the Universe evolves from simplicity and disorder to complexity and order via self-organization, in accordance with the empirical laws of nonequilibrium thermodynamics.[29]

Biological cells qualify as non-equilibrium thermodynamic open systems, appropriating some of the energy flowing past them, using 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 of the universe. 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.[10] [30]

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.[31]

The sun (Sol) supplies much of the energy gradient that sources thermodynamic disequilibrium for living systems on earth. However, as Benner et al.[22] point out:

> ...heavier atomic nuclei, left from a supernova, are not at thermodynamic equilibrium. Decay of these nuclei is a powerful source of planetary not-at-equilibrium environments. Radioactive decay [deep in Earth] drives tectonics and volcanism on Earth. These create non-equilibrium environment in many areas such as black smokers on the ocean floor. The consequent energetic disequilibrium supports life [near them] despite the absence of direct solar energy.[22]

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:[32]

Thermodynamic principles thus contribute not only to answering the question “what is life?” but also to “why is there life?”.[33] [34]

Sir Arthur Eddington, the astronomer who first confirmed Albert Einstein's general theory of relativity, remarked:

> The law that entropy always increases--the second law of thermodynamics--holds, I think, the supreme position among the laws of Nature. If someone points out to you that your pet theory of the universe is in disagreement with Maxwell's equations--then so much the worse for Maxwell's equations. If it is found to be contradicted by observation--well, these experimentalists do bungle things sometimes. But if your theory is found to be against the second law of thermodynamics I can give you no hope; there is nothing for it but to collapse in deepest humiliation.[35]

Harold Morowitz and Eric Smith begin their essay on that perspective as follows:[21]

> 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.[21]

See also commentary on Professors Morowitz and Smith's article.[36]

> Morowitz and Smith think that such order happens because it is a better 'lightning conductor' for discharging excess energy.[36]

Life is the transmutation of sunlight.

It is the energy and matter of the sun become the green fire of photosynthesizing beings. It is the natural seductiveness of flowers. It is the warmth of the tiger stalking the jungle in the dead of night…
As life transmutes solar fire into all the material and energetic cycles of the biosphere, we pay homage to the ingenious ascension of the living plant.
--Lynn Margulis and Dorian Sagan [37]

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.[38] 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 volcanic 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:

A living system:

* Has the ability to remain for a long time as an organized system
* The persistence of the organized state depends on the system's location within an energy gradient, a flow of energy from a more to a less concentrated state, like sunshine and hot springs
* Energy flows because probability ever drives concentrations of energy toward the more probable state of maximal dilution
* That downhill flow of energy provides a living system with energy and energy-rich matter
* Ultimately the energy flow drives the system to build and re-build its organized state
* The drive comes because the work of building organization causes the system to export wastes to its surroundings in the form of low-energy heat and unusable matter
* The work-waste of thusly degraded energy increases the degree of disorder of the system's surroundings, else without the system's work, the surroundings would have more order as more concentrated energy
* Empirically known, creating order through work in one place creates more than compensatory disorder elsewhere
* Thus in creating living order, the degree of disorder of a living system plus its surroundings increases -- a cost of living
* In that way the system uses available energy to build and maintain an organized state far from its final equilibrium state of minimal energy and order
* A living thing not only obeys the Second Law of Thermodynamics, but also facilitates the operation of the Second Law by actively dissipating energy gradients

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."[39] [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[edit]

A reasonable answer to the question ‘What is life?,’ then, seems to be: an embodied metabolism...
—Ed Regis, Science Writer

Broadly specified, metabolism encompasses the combined results of all of the body´s chemical reactions and interactions that enable living:

* those that manage the energy exchanges of the living system, including capturing energy from outside the system, converting and inter-converting it to a variety of forms for differing physiological activities, and disposing of non-utilizable energy waste outside the system;
* those that manage the dynamic architectural and functional status of the system through molecular reactions, for signalling, synthesis, and degradation; and,
* those that manage disposal of waste molecular material;

-- in short, the combined results of all of the body´s chemical reactions and interactions that manage persistence of the living system as a dynamic functioning entity, in particular functioning to support a self-assembling, self-organizing, developing, adapting, self-reproducing entity.

Some definitions 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.[40]

> Although a living organism is identified and recognized by its physical appearance, and hence by its structure, its status as living is defined by its chemistry, and thus by its metabolism. This is a network of reactions that is responsible for synthesizing all of the molecules needed for the organism to survive, apart from those directly available from its environment, and for disposing of molecules that are harmful or no longer required. The entire network consists of thousands of connected reactions, and as many of these need to be maintained far from equilibrium, all organisms require and consume energy. [41]

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? If so, we must include in metabolism all of the physics and chemistry enabling self-assembly, self-organization, homeostasis, allostasis, network regulation, gene regulation, and much more. Does 'metabolism' adequately describe the phenomenon of emergent behavior of living systems, however essential we recognize metabolism for the existence of a living system?

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[42][21] recognize a “core metabolism” in all living systems and characterize it as follows:

> ....we know from analysis of entire genomes (citation to:[43]) 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:[44])[21]

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:[45])[21]

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."[21]

Smith and Morowitz propose:

> ....that rTCA [the reductive tricarboxylic acid cycle] is statistically favored among competing redox relaxation pathways under early-earth conditions and that this feature drove its emergence and also accounts for its evolutionary robustness and universality.[42]

The core structurally-creative anabolic (energy-storing) network observed in autotrophs 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.[46]

### Evolutionary aspects of 'living'[edit]

It is interesting to contemplate an entangled bank, clothed with many plants of many kinds, with birds singing on the bushes, with various insects flitting about, and with worms crawling through the damp earth, and to reflect that these elaborately constructed forms, so different from each other, and dependent on each other in so complex a manner, have all been produced by laws acting around us. These laws, taken in the largest sense, being Growth with Reproduction; Inheritance which is almost implied by reproduction; Variability from the indirect and direct action of the external conditions of life, and from use and disuse; a Ratio of Increase so high as to lead to a Struggle for Life, and as a consequence to Natural Selection, entailing Divergence of Character and the Extinction of less-improved forms. Thus, from the war of nature, from famine and death, the most exalted object which we are capable of conceiving, namely, the production of the higher animals, directly follows. There is grandeur in this view of life, with its several powers, having been originally breathed into a few forms or into one; and that, whilst this planet has gone cycling on according to the fixed law of gravity, from so simple a beginning endless forms most beautiful and most wonderful have been, and are being, evolved.

--Charles Darwin, Last Paragraph, Origin of Species, 1st ed.

In the human 'poetic/animistic' imagination, living systems include fires and storms. The flames of candles, forest fires, and tornadoes do qualify as non-equilibrium open systems -- like the living systems of the three recognized domains of life, Archaea, Bacteria, and Eukarya -- but they lack the essential activities of living systems, all of the activities required to perpetuate the informational base they constitute. Fire can spread and split, as in large forest fires, but they eventually all die out without leaving any progeny to perpetuate their informational nature, as the trees of the forest do; forests restore their former diversity and biomass after the fire dies out. Today's forest fires carry no inherited information from the forest fires of ancient times, because those ancient fires did not possess the intrinsic self-organized mechanism for replicating and re-replicating itself, generation upon generation, an inherited mechanism, like the forest trees possess, enabling them to make copies of themselves to keep populated the forest with trees after they die out, or to re-populate it after a fire.

Fires all become fire entities spontaneously, but separately, independently, without continuity over millennial time. Tornadoes, tempests in a teapot. Fires and tornadoes haven't designed themselves to maintain continuity after their death, unlike the living things comprising the three recognized domains of life.

When a living system reproduces itself, ensuring its informational continuity, its offspring inherit its properties, but the offspring may acquire new properties and lose other ones along the course of the inheritance pathway, imperfect fidelity of informational reproduction, variations on the inherited property profile caused by random events. Some variations offer some of the offspring[47] less opportunity to reproduce than others, and other offspring better opportunity, sometimes better even than their parents. Accordingly, new groups with different heritable property profiles arise that may supplant older groups because of greater reproductive fitness.[48] Biologists call this evolution by "natural selection", or by "survival of the fittest", and many regard it as the most important way whereby living systems evolve over geological time.

The causes of the heritable property profile variations play a role in determining species evolution. Chance plays an influential role there. Natural experiments, like endosymbiosis, a chance event, play an important role in evolution, allowing natural selection the opportunity to select among new endosymbiotic species.[49] Epigenetic transmission of information can introduce property profile variations that persist across generations, so might contribute to evolution by means of natural selection.[50] [51] Heritable properties subject to profile variations invite natural selection to act if the variations cause differences in reproductive fitness.

Evolution of living systems across reproductive generations requires variations in heritable property profiles capable of influencing reproductive fitness in circumstances where competition for reproductive fitness determines who gets to reproduce most fecundly.

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, one that enables descent with modification, allowing living systems to adapt to changing circumstances that determine what counts as reproductive fitness, and so perpetuation of a lineage.[49] [51] [50] Evolution by natural selection will occur if heritable variations produce offspring that differ in their reproductive fitness and if circumstances induce competition among conspecifics for reproductive fecundity. 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.[49]

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:[52] 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.[53]

When it comes to the fundamental structures and processes of living, however, some biologists argue against the requirement for reproduction.[54] NASA defines 'life' as a "chemical system capable of Darwinian evolution", without specification of reproduction per se (for discussion, see Benner et al.[55]).

Adding to the thermodynamic perspective, we might say that:

A living system:

* Has the ability to maintain its self-organized state of living by producing copies of itself.
* In so doing it subjects itself as a species to mechanisms that may adapt it to a changing environment.
* In so doing it participates in trans-generational evolutionary changes of the species to which it belongs.

### Self-organization[edit]

As the wind of time blows into the sails of space, the unfolding of the universe nurtures the evolution of matter under the pressure of information. From divided to condensed and on to organized, living, and thinking matter, the path is toward an increase in complexity through self-organization..

--Jean-Marie Lehn

A self-organizing system may be characterized by global, coordinated activity arising spontaneously from local interactions between the system's components. This activity is distributed over all components, without a central controller supervising or directing the behavior. Self-organization relates the behavior of the individual components (the microscopic level) to the resulting structure and functionality of the overall system (the macroscopic level). Simple interactions at the microscopic level may give rise to complex, adaptive, and robust behavior at the macroscopic level.

--Fifth International Workshop on Self-Organizing Systems (IWSOS 2011) KIT, Karlsruhe, Germany, February 2011.

The order we find in living systems results to a large degree from the ability of the system to organize itself, independently of a master controller, program director, blueprint, algorithm, or template. Self-organization 'emerges' as a spontaneous manifestation of the interactions among the systems' components, and of the interactions of the system with the environment embedding it -- in effect, it emerges as computational information processing, reflecting the past influence of the processes of natural experiment and natural selection.

In cells, self-organization emerges in part from so-called intermolecular or supramolecular (non-covalent) interactions of proteins-with-proteins and proteins with other molecules.[56] [57] [58] 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. Jean-Marie Lehn, of the Institut de Science et d'Ingénierie Supramoléculaires, Université Louis Pasteur, summarizes it in this way:

> A self-organization process may be considered to involve three main stages: (i) molecular recognition for the selective binding of the basic components; (ii) growth through sequential and eventually hierarchical binding of multiple components in the correct relative disposition; it may present cooperativity and nonlinear behavior; and (iii) termination of the process, requiring a built-in feature, a stop signal, that specifies the end point and signifies that the process has reached completion.[56]

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.[57] [59] To quote Reinhout and Crego-Calama:[60]

> 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...

Again, J-M Lehn:[61]

> 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 only in part from supramolecular interactions, proteins with proteins and other molecules, reflects the involvement not only of supramolecular self-assembly but also of evolutionary mechanisms, operating on random variation through selection of molecules and networks of molecules that tend to optimize the fitness of functional self-organization — in other words, Darwinian evolution, or adaptation, operating to influence the nature of the self-organizing process.

Many workers (see: Hoelzer et al. [62]) emphasize self-organization as playing an explanatory role for the process of natural selection: "….it is clear that the process of SO represents a potential explanation for adaptive biological evolution." Hoelzer et al. discuss that in terms of the physics of self-organizing processes -- the extraction of work through channeling free energy gradients -- showing that a similar physics applies to the process of natural selection, rendering self-organization and natural selection complementary processes in sustaining living complex adaptive systems.

One must also invoke local real-time selective processes that confer stability and appropriate functionality to self-assembly, called homeostasis or adaptability. Thus, order emerges out of chaos.[63]

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.[64]

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.[65]

One way to understand this self-organization is to view a living system as a 'computing device'. The inherited and acquired information base -- the genome -- specifies components which arrange themselves in accord with their physico-chemical properties -- i.e., they 'compute' the system in a complex chemical reaction. Systems biologist, Denis Noble, incisively describes it:

> Genes code for protein sequences. They do not explicitly code for the interactions between proteins and other cell molecules and organelles that generate function. Nor do they indicate which proteins are on the critical path for supporting cell and organelle function in health and disease. Much of the logic of the interactions in living systems is implicit. Wherever possible, nature leaves that to the chemical properties of the molecules themselves and to the exceedingly complex way in which these properties have been exploited during evolution. It is as though the function of the genetic code, viewed as a program, is to build the components of a computer, which then self-assembles to run programs about which the genetic code knows nothing...[66]

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.[66]

The molecular biologist Sidney Brenner[67] [68] 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.[69]

The structure and behavior of self-organized systems need no behind-the-scenes '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".[70]

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."[71]

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

A living system:

* Organizes itself into a spatio-temporal dynamic system
* Such self-organization happens as a spontaneous manifestation of the physico-chemical interactions among the system's components, influenced by the larger system embedding it, and by that systems interactions with its environment

### Autonomous agents[edit]

[C]onsider a bacterium swimming upstream in a glucose gradient. We would, and do, all say that the bacterium is going to get food. That is to say, the bacterium is acting on its own behalf in an environment. I will call a system that can act on its own behalf in an environment an 'autonomous agent'.

-- Stuart Kauffman[72]

Stuart Kauffman uses the concept of 'autonomous agents' to explain living systems.[72] [73] 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.[72]

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.[72]

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.[74]

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."[75] 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:

A living system:

* Has the ability to work autonomously, in own behalf with its own agenda, to offset disorganizing perturbations
* It does so in virtue of its construction from many molecular autonomous 'agents' working in concert
* It is enabled to do so in virtue of the external energy it feeds on and its ability to utilize that energy to perform cyclic molecular work

### Networks[edit]

(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.[76]

The science of networks[77] 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.[77] [78]

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."[79] 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.[80] 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. [81] [82]
* 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.[83]
* 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.[84] In several well-studied biological networks, the abundance of network motifs -- small subnetworks -- correlates with the degree of robustness.[85] Networks, like those in cells and those in neural networks in the brain,[86] 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.[84]

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.[87] 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:

A living system:

* Has the ability to generate its dynamic self-organization as a system of hierarchical robust modular networks.

### Information processing[edit]

....I shall argue that this information flow, not energy per se, is the prime mover of life--that molecular information flowing in circles brings forth the organization we call "organism" and maintains it against the ever-present disorganizing pressures in the physics universe.

--Werner R. Loewenstein[65]

It seems probable that thermodynamic information derived from free energy was the driving force behind the origin of life. It is today the driving force behind all forms of life - behind the local order which life is able to produce. This is the "general law" which Darwin guessed might someday be shown to underlie the principle of life. All of the information contained in the complex, beautiful, and statistically unlikely structures which are so characteristic of living organisms can be seen as having been distilled from the enormous flood of thermodynamic information which reaches the earth in the form of sunlight.

-- John Scales Avery[88]

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, to develop computationally-based products to offload human cognitive loads and enhance human cognitive functioning,[89] etc.). Those realities attest that biological systems harbor, and perhaps fundamentally consist of information,[65] at least as people usually understand the 'information'.

Living systems not only harbor information useful to biologists, but they also acquire, generate, and employ information useful to themselves, as Lowenstein notes in the epigraph to this section. 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?

The word 'information' comes from the verb 'to inform', originally meaning to put form into something: the seal in-forms the wax, and the wax now contains in-formation. A random collection of particles or other entities has no form, nothing has given it form, and it contains no in-formation. The more randomness in the structure of the collection, the fewer improbable arrangements or interactions it has among its parts.

(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.[90]

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.[91]

Thus a living system emerges as an information processing system. It can receive information from energy[92] 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.[50] [49] [93] [51]

Physiologist and Director of the Laboratory of Cell Communication at the Marine Biological Laboratory, Woods Hole, Massachusetts, Werner R. Loewenstein[65] 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.[94] 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.[95] 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.[96] [97] 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.[98]

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.[99] 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:

A living system:

* Can generate its dynamic self-organization as a system of hierarchical robust modular networks because its possesses the informational content and information-processing ability to achieve those characteristics
* It receives it informational content by tapping the energy and matter-energy flow through the gradient it resides in, and by inheriting a molecular database from its ancestors
* It possesses its information-processing ability as a physico-chemical consequence of the interactions among its components
* Natural selection, and other evolutionary mechanisms, fine-tuned that information-processing ability

|

### Autopoiesis[edit]

In its broadest sense a living unit or entity is one that can direct chemical changes by catalysis, and at the same time reproduce itself by autocatalysis, that is, by directing the formation of units like itself from other, and usually simpler chemical substances.

--Jerome Alexander, Life: Its Nature and Origin 1948, Chap5, p79

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),[100] though first enunciated, as pointed out in 2007 by J-H S. Hofmeyr,[101] by the philosopher Immanuel Kant (1724–1804),[102] and adumbrated by twentieth century biologists before Maturana and Varela.[103].

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?[104]

Any entity, whether a cell or an ecosystem, that we recognize as living we recognize also as a 'living system' -- Kant's 'organism' in its broadest sense -- an assemblage of components, many copies of diverse types, 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 an 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, all driven by physico-chemical principles, including the laws of thermodynamics.

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, and ability to adapt to adversity and to fortunate conditions --it qualifies as both a homeostasis machine and an allostasis machine, operating autonomously.

A living system’s homeostatic and allostatic abilities play a central role in defining its uniqueness, as it enables it to homeostatically and allostatically regulate the most important variables in concert required for its continued living: an organization, whatever its description, that perpetuates its existence as a living system autonomously. 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 self-perpetuating organization, if often through change. 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.[105]

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[100] 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:[106]

> \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 organization overwhelms its homeostatic ability, the machine self-reproduces.

By this view, neither growth nor reproduction necessarily constitute 'primary' abilities of living machines, as both occur, in life on Earth, as the consequence of the homeostatic adaptable activities of the self-constructing organization that fabricates components whose interactions realize that organization, along with its homeostatic adaptability. On other worlds, living systems need not necessarily grow or reproduce, so long as they can, in some way, fabricate the components that can self-organize to construct the organization that can fabricate those components, including the system’s own boundary whose character enables its individuality and access to resources and waste disposal.[107]

Scientists can model and even synthesize experimental living machines that satisfy the basic criteria of a self-constructing self-perpetuating homeostatic machine (see[106]).

Access to resources alone cannot carry the day for a self-constructing homeostatic machine. It must have the ability, as part of its self-constructed organization, to recognize the resources it needs in order to sustain its organization. Recognition, however mediated, implies a type of ‘cognition’. In that case, for living machines to have an organization that produces the components that self-construct their-own component-producing organization, that organization must devote some of its activities to a type of cognition that enables it to recognize resources and import them and dispose of waste.

Those considerations dictate that a full description, or definition, of a living machine include the following:

* An organization of components capable of producing and reproducing, cyclically, the components that self-organize to construct the organization of components that produces those components;

* The components produced self-construct a boundary between the machine and the environment, of a nature that enables the machine to trade with the environment, acquiring the materials and/or energy required to sustain its self-perpetuating organization;

* The components produced self-construct an organization that has the cognitive ability to recognize the resources it needs to import and the wastes it needs to export.

* The components produced self-construct an organization that has the homeostatic ability to ‘correct’/’accommodate’ perturbations of the organization, or to reorganize appropriately to sustain a self-perpetuating organization;[108]

With those conditions realized, we can then ask about the details of the mechanisms or conditions that effect that realization in Earth’s living machines, whose components are molecules that self-construct networks comprising an organization that recursively constructs its components of such nature that the organization they produce can operate autonomously with homeostatic adaptability to sustain or reorganize itself as a cognizing compartmented system capable of escaping thermodynamic equilibrium through repeated self-reproduction.

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

A living system:

* Has the characteristics of a cognizing living machine
* Its organization of components fabricate, and re-fabricate, the components that self-organize to construct the very organization of components that fabricates those components -- unlike non-living machines
* It cognizes, through a variety of mechanisms, its own needs for self-fabrication

### A hierarchy of emergent systems[edit]

(See Systems biology)

Every object that biology studies is a system of systems.

--Francois Jacob (1974) The Logic of Living Systems: a History of Heredity ISBN 0713903600

There is a certain amount of naivety to the idea that for any process — be it biology or weather prediction or anything else — you can simply take very large amounts of data and run a data-mining program and understand what is going on in a generic way.”

-- Leonid Kruglyak, geneticist[109]

A systems perspective of 'living' recalls Aristotle's four components of causality,[110] [111] [112] in that a living thing comprises:

* A list of organic and inorganic parts (e.g., molecules and ions; cells, organelles, organs and organisms) -- Aristotle’s 'material' cause;
* How the parts relate to each other to form structures (e.g., networks) -- Aristotle’s 'formal' (form-like) cause;
* How the parts and structures interact with each other (e.g., network dynamics), and how they interact in a coordinated dynamic and hierarchical manner (e.g., gene expression; self-organization; competition) -- Aristotle’s 'efficient' (effect-producing) cause; and
* How the living system as-a-whole functions and behaves, and the properties that characterize it (e.g., reproduction; locomotion; cognition) -- Aristotle’s 'final' cause

The analysis of all of those components together forms part of the new discipline of Systems Biology.

###  Emergence[edit]

Systems biologists study, among other things, the phenomenon of 'emergence', whereby properties, functions and behaviors of living systems arise though not exhibited by any individual component of the system, and, importantly not expected, explainable or predictable from complete understanding the components' properties/behaviors considered in isolation from the system that embeds them, and in isolation from the environment that embeds the system. Every cellular system exhibits emergent behaviors. Emergent behaviors of living systems include such things as locomotion, sexual display, flocking, and conscious experiencing. Even the biological components of living cells, such as mitochondria and other organelles, exhibit emergent properties.

Some biologists might find it tempting to see a type of 'vitalism', or 'life force', in living systems, given that some whole-system properties/behaviors of organisms, including even the activity of living itself, exemplify such emergent phenomena. One could not explain, for example, the action of an organism fleeing from a predator from a study of the properties of an organism's component subsystems. The properties of the component parts depend on the organization of those parts in the whole system, including the system's environment. Because biologists and their co-scientists can sometimes explain emergent properties/phenomena, if only in principle, by mechanisms that do not transcend interactions of energy, information, and matter, any such 'vitalism' properly qualifies only as a 'materialistic vitalism'.

One example of emergence: When components of a signaling pathway, which enable between-cell communication, interact to form the signaling system, properties can emerge -- such as a self-sustaining feedback loop and generation of the signals themselves -- that one cannot explain from the individuated properties of the separate components of the system.[113]

For another example, in studying a protein separated from the system it belongs to, one can observe many of its properties, but in so studying the protein one cannot explain any of the properties it has only in the context of the system that embeds it, such as the property of catalyzing a biochemical reaction, or of binding to other proteins to form a functional protein complex. Those properties of the protein emerge in the context of the protein’s environment -- how it interacts in the context of the system as a whole. Moreover, those emergent properties may result in effects within the system that, in a feedback way, further alters the properties of the protein in the system, as when a reaction product alters the catalytic properties of the protein.

Why do not all of the properties/behaviors of a system predictably result from the properties of its components? After all, the reductionist paradigm that dominated the Scientific method in the 20th century operated on the exactly opposite assumption. For one thing, the intrinsic properties of a system’s components themselves do not determine those of the whole system; rather, their 'organizational dynamics' does -- how the components interact coordinately in time and space. Those organizational dynamics include not only the interrelations among the components themselves, but also interactions among the many different organizational units in the system.

For example, physical chemists cannot predict the properties of water from knowledge of its components, hydrogen and oxygen. The way hydrogen and water interact to form H2O, and the way H2O molecules interact, enables the properties of water to 'emerge'.[114] Secondly, the living system always operates in a certain context (its external environment, or surroundings), and those surroundings, in turn, always affect the properties of the system-as-a-whole. For example, nutrient gradients in its environment influence the direction a bacterium’s locomotion. The impact of environmental context affects the dynamic organization of the components within the system -- a 'downward causation'. Following up on the example of water, the properties of its environment (e.g., temperature, pressure) affect the way the H2O molecules organize themselves, as ice, or liquid, or steam For another example, environmental signals can activate or suppress a metabolic pathway, reorganizing cellular activity.

In relation to downward causation, the environment’s effect can sometimes reach down to the genetic database with molecular signals, altering its expression and consequently the characteristics of the cells without altering the database itself -- so-called 'epigenetic' effects. When epigenetic alterations of gene expression occur in the reproductive organs, the system changes can be transmitted to the next generation.[115] [116] One cannot simply take a living system apart and predict how it will behave in its natural environment.

As Gilbert and Sarkar[117] put it: "Thus, when we try to explain how the whole system behaves, we have to talk about its parts the context of the whole and cannot get away talking only about the parts."

> …picture reductionism as a system where a “bottom-up” approach (e.g., atoms to molecules to organelles to cells to tissues) is sufficient to explain all phenomena. Organicism claims that this is not sufficient and that top-down and bottom-up approaches must both be used to explain phenomena. For instance, reductionistic ontology and explanations would see a tissue as an organized collection of cells and cells as an organized collection of organelles, etc. Organicist ontology and explanations would include those bottom-up considerations but would also include the functioning of the tissue within the organism, the functioning of the organism within its environment (and, perhaps, other parameters as well). The structure and function of a hepatocyte depends not only on the properties of organelles comprising it, but also on the properties of the organ in which it resides.[117]

Philosopher of science D.M. Walsh puts it this way: "The constituent parts and processes of a living thing are related to the organism as a whole by a kind of 'reciprocal causation'."[118] In other words, the organization of the components determine the behavior of the system, but that organization arises from more than the set of its internal components. How the whole system behaves as it interacts with its environment determines how those components organize themselves, and so novel properties of the system 'emerge' that characterize neither the environment nor that set of internal components. The behavior of a human kidney cell depends not only on its cellular physiology, but also on all the properties of the organ (kidney) which constitutes its environment. The kidney's overall structure and function influence the cell’s structure and behavior (e.g., by physical confinement and by cell-to-cell signaling), which in turn influence the organization of its intracellular components. The kidney in turn responds to its environment, namely the individual body that it lives in, and that body responds to its environment, which includes such factors as the availability of particular food items, fresh water, and ambient temperature and humidity. Systems biologists regard emergent properties as arising from a combination of bottom-up and top-down effects -- Walsh's 'reciprocal causation'.

Using the example of termites out of whose combined individual behaviors without outside management emerge complex colony mounds, a recent National Research Council report on the role of theory in advancing 21st century biology commented on emergent behavior as follows:[119]

> A reasonable way of thinking about emergent behavior might be to focus on the level or scale at which the rules reside. If the rules are specified at a low level, for example, the individual termites, and the patterns and structures, like termite mounds, emerge at a scale where there are no rules specified, we may call this emergent behavior.[119]

Other examples of rule-free emergent behavior for which the 'rules' appear specified at a lower level than the emergent behavior itself include the flocking behavior of birds, and the folding of amino acid polymers into catalytic proteins.

###  Spectrum of emergence in biology[edit]

Emergent processes have been recognized as, for example, contributing to understanding:

* Subcellular morphology,[120]
* Developmental biology,[121] [122]
* Metabolic networks [123],
* Proteomics,[124] [125]
* Evolution of complexity in living things.

Emergent phenomena appear even in non-biological physical systems. [126] Emergent phenomena attract the attention of cellular neuroscientists; [127] and cognitive scientists [128].  At still higher systems levels, emergent properties appear for example in the behaviour of ant colonies and the concept of swarm intelligence, [129] Systems scientists have simulated emergent phenomena [130] Emergent phenomena in human societies has also received attention. [131].  Biologists even explain the biosphere itself as emergent.[132] Emergent systems always display what we recognize as 'complexity', a feature we have a difficult time precisely defining. Complex systems appear to require more bits of information (words, sentences, lines of computer code, etc.) to describe than the bits of information in the system itself. [133] The operation of the system itself supplies its own most economical model.

According the paleontologist and origin of life researcher, Robert Hazen, four basic complexity elements underpin emergence in a system: [134]

* A sufficiently large 'density' of components, with increasing complexity as the concentration increases, up to a point;

* Sufficient inter-connectivity of the components, with increasing complexity with greater and more varied types of inter-connectivity, up to a point;

* A sufficient energy flow through the system to enable the system’s components to perform the work of interacting in the self-organized way characteristic of the energized system;

* Flow of energy through the system in a cyclic manner, presumably facilitating the spatio-temporal patterning characteristic of organized systems.

Living systems thus generate complexity and emergent properties as a hierarchy of emergent subsystems embedded in even more complex emergent systems, as in the case of an organism living in an environment of other organisms.

Further elaborating on the several perspectives of living systems described above, we may say that:

A living system:

* Generates novel properties, functions and behaviors at all levels of its organization
* Those novelties at any given level of organization emerge from interactions of the components comprising it, influenced by the combined effects of the properties of the subsystems it embeds and those of the larger systems that embed it

## Fundamental underpinning of living systems[edit]

### Different scientific perspectives[edit]

...life is an obligatory manifestation of the combinatorial properties of matter...

—Christian De Duve, Vital Dust

The different perspectives biologists use in viewing living systems can be identified as follows:

* Living systems import free energy, energy-rich matter, order (sometimes called 'negentropy') and information from their environment, and export waste in the form of low-grade, degraded energy, unusable materials, and more disorder (entropy) than the order they generate within themselves. The downhill flow of free energy through a living system enables that sequence, enables living systems to organize themselves and sustain that organization, and thus to delay (for their lifetime) the dictate of the Second Law of Thermodynamics, which states that organized systems ultimately degrade to a state of randomness;

* The basic building blocks and working units of all living systems are cells, separated from their surroundings by a boundary membrane that allows energy, material and information exchange with their surroundings; one may think of cells as the 'atoms' out of which living systems structure and functionalize themselves, atoms of many types, more than the number of chemical elements, most atom-cells consisting of numerous 'isotopes' in the form of slightly differing 'genotypes';

* All cells derive from cells and therefore begin life with a basic starter set of cellular machinery;

* As part of their starting materials, cell inherit a (genetic) database to draw upon for self-organization. That source of information, in the form of nucleic acid macromolecules, encodes many different types of proteins that interact according to their natural physico-chemical properties to self-assemble an organization of hierarchically arranged subsystems that can import energy and export waste;

* Cells inherit genetic and other forms of heritable information from 'parent' cells, raising as yet unanswered questions: how did cells arise in the first place? and how did they acquire stores of information?[135] (see Origin of life and Evolution of cells)

* The molecular and supramolecular interactions that self-assemble and sustain the living organization are governed by the universal laws of physics and chemistry; those laws, together with inherited information, enable a self-organizing system that can work autonomously in its own behalf, for persistence of the living state and for reproduction, and allow properties and physiological functions to emerge that study of the properties of the system's constituent parts isolated from the system embedding them could not have anticipated;

* The activities of a living system have no 'master controller'; they need only a type of organization, self-assembled, that maintains the system far-from-equilibrium, a state often yielding improbable self-organized novel structures and activities;

* Living things cannot escape from real-time changes in external conditions, so they must maintain homeostasis, real-time adaptability beyond the limits of homeostasis (viz., allostasis), adaptable enough to reorganize to sustain their living state, and exhibit robustness in their organization. Robustness and adaptability derive from the properties of a hierarchical network of subnetworks of molecular circuits;

* Living systems generate complexity and emergent properties as a hierarchy of emergent subsystems embedded in even more complex emergent systems, as in the case of an organism living in an environment of other organisms.

* Living systems produce enough variability during reproduction to allow evolution through natural selection, which guides the continuation of a 3.5 billion year history of Earth’s living world. By evolution, living systems generate increasing varieties of living systems, occupy an extreme spectrum of environments, create their own environments that influence their own evolution and that of other species,[136] and develop sufficient complexity to enable them to process information in a way that allows them to 'experience' themselves.

### Synthesis of perspectives[edit]

The eternal mystery of the world is its comprehensibility...

--Albert Einstein

(CC) Image: Chris Day
Signs of life. Top: Spermatozoon and oocyte merge to begin a new building block for a living system. Middle: DNA, the database for the construction of life's protein components. Bottom: Life as humans describe it in books.

The activity of living depends on the ability of the living cell-based system to generate and sustain quasi-steady-states of self-fabricated. self-assembled, and self-organized functioning far from a state of randomness, and its ability to respond to internally and externally derived conditions that perturb its current quasi-steady-state by making adjustive responses, including maintenance of homeostasis, resetting of homeostatic set-points through allostasis, self-reorganization (as in growth and development) and self-reproduction

The system attains those abilities partly and critically because of its location in the path of a downhill gradient of flowing free energy, including that stored in energy-rich molecules. It can draw off some of that downflow of energy by importing it, and it can export the inevitable wastes of degraded energy and materials it generates in performing the activities that keep it alive. It thereby generates, sustains and increases its own highly ordered and improbable state at the expense of a more than counterbalancing, more probable disordered state of its surroundings.

An organism lives by importing and utilizing free energy and by generating and exporting entropy.

Those principles seem to apply to all living systems: single cells, multicellular organs and organisms, and to biological systems whose parts are living systems: multi-organism demes and ecosystems. The fundamental challenges to staying alive do not differ greatly for an amoeba from those of a human. Neuroscientist Antonio Damasio[137] puts it this way:

> All living organisms from the humble amoeba to the human are born with devices designed to solve automatically, no proper reasoning required, the basic problems of life. Those problems are: finding sources of energy; incorporating and transforming energy; maintaining a chemical balance of the interior compatible with the life process; maintaining the organism's structure by repairing its wear and tear; and fending off external agents of disease and physical injury.[137]

Professor Damasio neglected to stress the critical feature of the organism's ability to generate and export entropy -- to a greater extent than it reduces its internal entropy. Without that ability, an internal entropy build-up would randomize it to premature death, and without that ability it would never have come to exist in the first place.

Steven Benner, Alonso Ricardo and Matthew Carrigan boil life down to this:

> We propose that the only absolute requirements [for life] are a thermodynamic disequilibrium and temperatures consistent with chemical bonding.[22]

With those requirements met, living things can emerge and persist.

The building block and working unit of all living systems is the cell. For cells to utilize available external energy or energy-rich matter to achieve and maintain a state of complex organization (order), they must have, from the outset, a basic informational content, a database. That database enables the cell to self-produce components that can, by natural molecular interactions, respond to the imported energy and energy-rich material to self-organize. That organization comprises modular networks of molecular interactions, and a hierarchy of interacting networks -- self-organized and coordinated functional interactions arising from chemistry and supramolecular chemistry. The properties of the networks and those of the hierarchy of networks enable the system to perpetuate itself, and to maintain its steady-state, or establish new steady-states, despite fluctuations in environmental factors. That principle, too, applies to all living systems. Any organism, plant or animal, comprises a network of organs working autonomously, maintaining and reorganizing its steady-state functioning far from equilibrium in response to environmental perturbations -- physiologists refer to those as homeostasis and allostasis..

One can view any living organism as an autonomous cognitive living machine functioning in its own behalf, i.e., without a master controller. It comprises an organization of components capable of producing and reproducing, cyclically, the components that self-organize to construct and reconstruct the organization of components that produces those components. The components self-construct a boundary between the machine and the environment, of a nature that enables the machine to trade with self-interest with the environment, acquiring the materials and/or energy required to sustain its self-perpetuating organization. The components self-construct an organization that has the cognitive ability to recognize the resources it needs to import and the wastes it needs to export. The components self-construct an organization that has the homeostatic ability to 'correct' perturbations of the organization, or to reorganize appropriately to sustain a self-perpetuating organization, including reproducing itself.

The networks that regulate the flow of information through the cell resulted from natural experiments refined and preserved by natural selection and other evolutionary processes. The databases it inherits, that evolved by natural experiment and selection, do not program living, but enable the living thing to self-produce the molecules that can interact in the very ways that contribute to self-organization of those networks that enable a cell to sustain and reproduce itself.

The collaboration of natural selection and physico-chemical laws perpetuates living systems not only in real-time but also in geological, or 'evolutionary', time. From common ancestors -- however they may have arisen (see Evolution of cells) -- informationally-guided, self-organizing, autonomous network dynamics enabled generation of the diversity of all living systems on the planet, over nearly four billion years. Living systems perpetuate living systems, exploiting free energy on its inexorable path to dissipation and degradation, and harvesting energy in developing organized systems by a more than counterbalancing dis-organizing of the larger system in which it is embedded.

#### Life abstracted[edit]

##### A non-Earth-centric non-matter-centric perspective[edit]

From the viewpoint of mathematics and physics, terrestrial life looks like an example (rather, a gigantic number of closely related examples) of what ought to be a far more general process. Many biologists feel the same way: they dislike defining life in terms of what it is made of: what it does and how it works seem more appropriate and less limiting. It’s rather like having a mathematics that is limited to numbers between 1 and 100, and wondering whether a more general concept of number could preserve most of the interesting properties observed in that range.

--Ian Stewart[138]

The activities, or processes, that render an entity living consist in an information dynamic that enables the entity to persist as an open system, far from thermodynamic equilibrium, doing so by enabling it to acquire energy in excess of the energy expended in the acquisition process, and to utilize that energy to power itself to work cyclically to regenerate continually short-lived components whose interactions in hierarchically structured dynamic networks enable it to operate without a central controller, as a self-assembled, self-organized, self-learning entity, one that performs emergent activities autonomously, in its own behalf, as necessary for sustaining its viability, including modifying its organization in adaption to threats to its operational viability.

##### An Earth-centric matter-centric perspective[edit]

On Earth, the information dynamic that spontaneously renders itself living consists in bits, or vibrating strings, arranged as code, manifesting via matter--it from bit--atoms making up the structural components. Energy from atomic nuclear reactions, flowing downhill from solar and geothermal sources, directly or indirectly drive electron and proton flows through matter pathways, converting the radiating energy into chemical energy that powers the work of living.

## Supplementary text[edit]

See Life/Addendum for supplementary text pertaining to this article, on these topics:

* Selected definitions of life
* Published collections of definitions of life
* The exobiologists view
* The gray zone
* Some modern views of the four Aristotelian causes of living things

## References[edit]

#### Citations and notes[edit]

Most citations to articles listed here include links to full-text. Accessing full-text may require personal or institutional subscription. Nevertheless, usually the links will show the abstracts of the articles, free without subscription. Links to books variously may open to full-text, or to the publishers' description of the book with or without downloadable selected chapters, reviews, and table of contents. Books with links to Google Books often offer extensive previews of the books' text.

1. ↑ From: Robinson R. (2007) Both barriers and trait complementarity govern pollination network structure. PLoS Biol 5(2):e54.
2. ↑ 2.0 2.1 2.2 Keller EF. (2002) Making Sense of Life: Explaining Biological Development with Models, Metaphors, and Machines. Cambridge, MA: Harvard University Press. ISBN 067400468. | Google Books preview.
3. ↑ Luisi PL. (2003) Autopoiesis: a review and a reappraisal. Naturwissenschaften 90:49-59 PMID 12590297.
* Note: The concept of autopoiesis incorporates within its scope of explanatory narrative many, if not all, of the fundamental characteristics of all living systems.
* From the Abstract: The basic principles of autopoiesis as a theory of cellular life are...described, emphasizing also what autopoiesis is not: not an abstract theory, not a concept of artificial life, not a theory about the origin of life--but rather a pragmatic blueprint of life based on cellular life. [Emphasis added] [T]his view leads to a conceptually clear definition of minimal life and to a logical link with related notions, such as self-organization, emergence, biological autonomy, auto-referentiality, and interactions with the environment. The perturbations brought about by the environment are seen as changes selected and triggered by the inner organization of the living. These selective coupling interactions impart meaning to the minimal life and are thus defined by Maturana and Varela with the arguable term of "cognition". This particular view on the mutual interactions between living organism and environment leads these authors to the notion of "enaction", and to the surprising view that autopoiesis and cognition are two complementary, and in a way equivalent, aspects of life. It is then shown how cognition, so defined, permits us to build a bridge between biology and cognitive science.
4. ↑ 4.0 4.1 De Duve C. (2004) Life Evolving: Molecules, Mind, and Meaning. Oxford University Press. New York ISBN 0195156056 Questia Online Library: Full-Text Online with Subscription. | Preview of book on Google books..
5. ↑ Szostak JW. (2012) Attempts to define life do not help to understand the origin of life. J.Biomol.Struct.Dyn. 29(4):599-600.
6. ↑ Davies PCW, Gribbin JR. (2007) The Matter Myth: Dramatic Discoveries That Challenge Our Understanding of Physical Reality. Simon & Schuster: New York. ISBN 9780743290913 (pbk). Preview book online at Google Books here.
* Excerpt: Quantum physics undermines materialism because it reveals that matter has far less "substance" than we might believe….matter as such has been demoted from its central role, to be replaced by concepts such as organization, complexity and information.
7. ↑ Grant MC. (1993) The Trembling Giant. Discover Magazine, October 1st
* From the article: Yet even the majestic giant sequoia is not the record holder. That honor goes to a tree that my co-workers and I have studied for years: the quaking aspen, a common tree that dapples many mountains of North America. Unlike giant sequoias, each of which is a genetically separate individual, a group of thousands of aspens can actually be a single organism, sharing a root system and a unique set of genes. We therefore recently nominated one particular aspen individual growing just south of the Wasatch Mountains of Utah as the most massive living organism in the world. We nicknamed it Pando, a Latin word meaning "I spread". Made up of 47,000 tree trunks, each with an ordinary tree’s usual complement of leaves and branches, Pando covers 106 acres and, conservatively, weighs in excess of 13 million pounds....
8. ↑ Zax D (2007) Champs. Smithsonian, Fall 2007. The General Sherman Tree
* According to Smithsonian author David Zax, as of 2006 a California sequoia, the General Sherman Tree, ranks as the world's largest living organism (52,500 cubic feet, 2.7 million pounds). The world's oldest, a California bristlecone pine, Methuselah, >4,800 years old.
9. ↑ Jones BW. (2008) The nature of life on Earth. Chapter 3. In: Barrie W. Jones. The Search for Life Continued: Planets Around Other Stars. Berlin: Springer, in association Chichester,UK: Praxis Publishing. ISBN 34567625464899467.
10. ↑ 10.0 10.1 D'Arcy Wentworth Thompson. (1992) On Growth and Form: The Complete Revised Edition Courier Dover Publication. ISBN 0486671356, ISBN 9780486671352. Original version, 1917.
11. ↑ Bains W. (2004) Many Chemistries Could Be Used to Build Living Systems. Astrobiology 4(2):137-167.
* In places in the universe where physical conditions might favor silicon-based macromolecules, silicon-based life might exist.
12. ↑ Ball P. (2005) Water and life: Seeking the solution. Nature 436:1084-5.
13. ↑ Tsytovich VN et al. (2007) From plasma crystals and helical structures towards inorganic living matter. New J Phys 9:263]
14. ↑ Interestingly, among the three domains of living systems , the predominant lipid species comprising the membrane differs. In most types of cells the predominant lipid species consist of molecules based on esters of glycerol combined with straight chain fatty acids, but in the Archaea domain it consists of ethers of glycerol combined with isoprene fatty components. That lack of membrane structural universality has implications for hypotheses on the origin of cells.
15. ↑ 15.0 15.1 Valentine JW et al. (1994) Morphological complexity increase in metazoans. Paleobiology 20:131-42
16. ↑ Woese CR et al. (1990) Towards a natural system of organisms: proposal for the domains archaea, bacteria, and eucarya. Proc Natl Acad Sci USA 87:4576-9
17. ↑ Baluska F et al. (2004) Eukaryotic cells and their cell bodies: cell theory revised. Ann Bot 94:9-32]

* Excerpt: ...those who are aware of the most recent advances in plant cell biology…are convinced that Cell Theory, as it now stands, is absolutely incompatible with a cell-based organization of higher plants…and requires an update....Indeed, formulation of organismal theory of plant development, in which it is stated that it is not the cell but the whole multicellular organism that is the primary unit of plant life....has precipitated a crisis for Cell Theory as applied to plants. A consequence of the fact that the cytoplasms of plant cells are interconnected via plasmodesmata is that the individuality of the cell is given up in favour of an integrated and corporate cytoplasm that benefits the whole organism. This supracellular, or organismal, approach towards multicellularity seems to have allowed sessile plants to adapt to life on land and to evolve even within hostile environments.
18. ↑ Note: Other boundaries of living systems include bark, shells, cell walls, skin, fur, and structures of the physical environment.
19. ↑ How Many Genes Are in the Human Genome? at the Human Genome Project Information website hosted by the U.S. Department of Energy
20. ↑ (a) The UniProtKB/Swiss-Prot Human Proteome Initiative; (b) Norregaard Jensen O (2004) Modification-specific proteomics: characterization of post-translational modifications by mass spectrometry. Curr Opin Chem Biol 8:33-41]
21. ↑ 21.0 21.1 21.2 21.3 21.4 21.5 21.6 Morowitz H, Smith E (2006) Energy flow and the organization of life Working Paper, Santa Fe Institute

* "Energy flow embeds life within the geosphere not just mechanistically but conceptually as an inevitable form of driven geochemical order."
22. ↑ 22.0 22.1 22.2 22.3 Benner SA, Ricardo A, Carrigan MA (2004) Is there a common chemical model for life in the universe? Curr Opin Chem Biol 8:672-89. PMID 15556414
23. ↑ The Second Law of Thermodynamics
24. ↑ Note: A random pattern of parts has no order (it has maximal entropy) and no information. A living system has order in its organized state; it has computationally-rich informational content, and low entropy.
25. ↑ Note: At birth -- the big bang -- the Universe received an energy account. The amount of energy remains forever constant, having distributed itself into many smaller accounts in a process in which the more compact and organized forms of energy -- the 'higher quality' energy of stars, for example -- disperses and degrades to a 'lower quality' energy, heat, or thermal energy. When the starting account finally becomes completely dispersed throughout the Universe in the form of randomly distributed colliding particles, (thermal energy, heat -- energy's most degraded and least useful form) no work will be possible, because no energy gradients (downward slopes) exist down which energy can flow to perform any work. At that point, the Universe will be at an equilibrium, characterized by a random distribution of the initial energy.
26. ↑ 26.0 26.1 Schneider ED, Sagan D (2005) Into the Cool: Energy Flow, Thermodynamics, and Life. Chicago: The University of Chicago Press. ISBN 0-226-73937-6 Chapter Excerpts and Reviews
27. ↑ Carnot S. (1825) Reflections On The Motive Power Of Heat And On Machines Fitted To Develop That Power
* Sadi Carnot (1796-1832), one of the founders of thermodynamics, understood that the capacity to do work by heat energy required a difference in temperature, an energy gradient. He wrote:

* ”The production of motive power is then due in steam-engines not to an actual consumption of caloric [quantity of heat], but to its transportation from a warm body to a cold body, that is, to its re-establishment of equilibrium…. According to this principle, the production of heat alone is not sufficient to give birth to the impelling power: it is necessary that there should also be cold; without it, the heat would be useless. And in fact, if we should find about us only bodies as hot as our furnaces, how can we condense steam? What should we do with it if once produced? We should not presume that we might discharge it into the atmosphere, as is done in some engines; the atmosphere would not receive it. It does receive it under the actual condition of things, only because it fulfils the office of a vast condenser, because it is at a lower temperature; otherwise it would soon become fully charged, or rather would be already saturated…. Wherever there exists a difference of temperature, wherever it has been possible for the equilibrium of the caloric to be re-established, it is possible to have also the production of impelling power.
28. ↑ Note:
* The words 'organize' and 'organization' appear often in this article, and so merit special note. When one organizes a collection of entities, one puts them in some kind of order, typically for some function. Functionality serves as the criterion for organization, or for an organized state of the entities. To organize, then, implies to structure parts in relation to one another for functionality.

* For living systems, nature inclines to organization. Often she structures the parts in 'dynamic' relation, such that the parts 'interact' temporally. The parts work together in a 'coordinated' and 'hierarchical' way that achieves a functionality that contributes to the naturally selected goals of a living system to survive in the living state and to manufacture new living systems like itself. 'Dynamic', 'coordinated', 'hierarchical', and 'goal-directed functionality' characterize 'organization' in biological systems. The words 'organize' and 'organization' should invoke those properties. Thus 'organization' connotes more than 'order' when it comes to living systems -- a special kind of order that achieves not only life-preserving functionality, but also unpredictable novelty, or emergent behavior. As we shall see, nature enables living systems to organize themselves.
29. ↑ Kurakin A. (2011) The self-organizing fractal theory as a universal discovery method: the phenomenon of life. Theoretical Biology and Medical Modelling 8:4.
30. ↑ Lotka AJ. (1922) Contribution to the Energetics of Evolution. PNAS 8: 147-151.
* Excerpt: Evolution, in these circumstances, proceeds in such direction as to make the total energy flux through the system a maximum compatible with the constraints...We have thus derived, upon a deductive basis, at least a preliminary answer to a question proposed by the writer in a previous publication.(cites: Lotka, A. J., Proc. Nat. Acad. Sci., 7, 1921, p. 172). It was there pointed out that the influence of man, as the most successful species in the competitive struggle, seems to have been to accelerate the circulation of matter through the life cycle, both by "enlarging the wheel," and by causing it to "spin faster." The question was raised whether, in this, man has been unconsciously fulfilling a law of nature, according to which some physical quantity in the system tends toward a maximum. This is now made to appear probable; and it is found that the physical quantity in question is of the dimensions of power, or energy per unit time, as was hinted by the writer on an earlier occasion.
* Note: Lotka invokes natural selection as facilitating energy dissipation (energy flow per unit time).
31. ↑ Prigogine I, Stengers I (1997) The End of Certainty: Time, Chaos, and the New Laws of Nature. Free Press, New York. ISBN 0684837056 Excerpt from Chapter 1; Table of Contents
32. ↑ (a) Swenson R, Turvey MT. (1991) Thermodynamic reasons for perception-action cycles. Ecol Psychol 3:317-48. (b) Swenson R. (1997) Thermodynamics, Evolution, and Behavior. In The Encyclopedia of Comparative Psychology G. Greenberg and M. Haraway (Eds), New York: Garland Publishers, Inc.
33. ↑ Schneider ED, Kay JJ (1994) Life as a manifestation of the second law of thermodynamics. Math Computer Modelling 19:25-48]
34. ↑ Note: If an energy gradient promotes the origin of living systems for the reason that as the energy flows through them they hasten the rate of entropy production of the Universe as a whole, by exporting more entropy to their surroundings than they reduce their internal entropy, then the energy gradient might also promote the development of complexity in living systems, as complexity further reduces a living system’s internal entropy (as greater organization). With sufficient organization, living systems can attain a degree of intelligence enabling them to fabricate energy-utilizing artifacts, like electrical lighting systems, fossil-fuel-based transportation systems, and solar and geothermal energy conversion to work. Those artifacts then would further contribute to dissipation of the life-promoting energy gradient and further accelerate the rate of entropy production of the Universe as a whole. Such considerations make it seem likely, most speculatively, that Nature’s abhorrence of energy gradients throughout the Universe would promote the origin and complexity development of living systems wherever physico-chemical circumstances permit, as a means of maximizing the rate of entropy production of the Universe as a whole.
35. ↑ Eddington AS. (1929)The Nature of the Physical World New York: The University Press, page 740. Full-Text, requires subscription.
* Also this passage and many excerpts of the book at: Google Books, page 74.
36. ↑ 36.0 36.1 Ball P. (2006) Was life on Earth inevitable? Nature Published online 14 November in NatureNews.
* Commentary on article by Morowitz and Smith. "Life may be the ultimate in planetary stress relief…[Morowitz and Smith] argue that life was the necessary consequence of available energy built up by geological processes on the early Earth. Life sprang from this environment, they say, in the same way that lightning relieves the accumulation of electrical charge in thunderclouds." In other words, say biologist Harold Morowitz of George Mason University in Fairfax, Virginia, and physicist Eric Smith of New Mexico's Santa Fe Institute, the geological environment "forced life into existence".
37. ↑ Margulis L, Sagan D. (2000) What is Life? Berkeley: University of California Press | Google Books preview.
38. ↑ Mehta P, Schwab DJ. (2012) The Energetic Costs of Cellular Computation. arXiv.org Quantitative Biology.
39. ↑ Nelson PC. (2004) W.H. Freeman and Company, New York ISBN 0-7167-4372—8
40. ↑ Hendrix ML. (2008) "Metabolism (chemistry)," Microsoft® Encarta® Online Encyclopedia http://encarta.msn.com © 1997-2008 Microsoft Corporation.
* ML Hendrix, Editor, National Institute of Mental Health. (Affiliation for identification only—does not imply NIH sponsorship.)
41. ↑ Cárdenas ML, Cornish-Bowden A. (2011) Metabolism (Biological). Encyclopedia of Astrobiology. Springer-Verlag Berlin Heidelberg.
42. ↑ 42.0 42.1 Smith E, Morowitz HJ. (2004) Universality in intermediary metabolism. Proc Natl Acad Sci U S A 101:13168-73.
* Abstract:

* We analyze the stoichiometry, energetics, and reaction concentration dependence of the reductive tricarboxylic acid (rTCA) cycle as a universal and possibly primordial metabolic core.
* The rTCA reaction sequence is a network-autocatalytic cycle along the relaxation pathway for redox couples in nonequilibrium reducing environments, which provides starting organic compounds for the synthesis of all major classes of biomolecules.
* The concentration dependence of its reactions suggests it as a pre-cellular bulk process.
* We propose that rTCA is statistically favored among competing redox relaxation pathways under early-earth conditions and that this feature drove its emergence and also accounts for its evolutionary robustness and universality.
* The ability to enhance the rate of core reactions creates an energetic basis for selection of subsequent layers of biological complexity.
43. ↑ KEGG. Kyoto Encyclopedia of Genes and Genomes
44. ↑ Lengeler JW, Drews G, Schlegel HG. (1999) Biology of the Prokaryotes. New York: Blackwell Science.
45. ↑ Eric Smith and Harold J. Morowitz. Universality in intermediary metabolism. Proc. Nat. Acad. Sci. USA, 101:13168–13173, 2004. SFI preprint # 04-07-024.
46. ↑ Braakman R, Smith E. (2013) The compositional and evolutionary logic of metabolism. Physical Biology 10:911001 (62pp). | Online at stacks.iop.org/PhysBio/10/011001.
47. ↑ Note: ....or the progeny of some conspecific living systems. Many living systems coexist with similar living systems, constituting a 'species', or group of 'conspecifics'.
48. ↑ Darwin C (1859) On the origin of species by means of natural selection, or the preservation of favoured races in the struggle for life. 1st edition.
49. ↑ 49.0 49.1 49.2 49.3 Reid RGB. (2007) Biological Emergences: Evolution by Natural Experiment. (With Table of Contents and Sample Chapters) A Bradford Book, Cambridge ISBN 0-262-18257-2 Additional Chapter Excerpts
50. ↑ 50.0 50.1 50.2 Jablonka E, Lamb MJ (2005) Evolution in Four Dimension: Genetic, Epigenetic, Behavioral, and Symbolic Variation in the History of Life. Cambridge: The MIT Press
51. ↑ 51.0 51.1 51.2 Goodwin B. (1994) How The Leopard Changed Its Spots: The Evolution Of Complexity Princeton University Press, Princeton. ISBN 0-691-08809-8 Excerpts of Multiple Chapters
52. ↑ Note:Some evidence supports the proposition that all extant living things (Archaea, Bacteria and Eukarya) descended from a common ancestor, though that common ancestor may have arisen from a proto-community of cells: "The common ancestor of eukaryotes, bacteria, and archaea may have been a community of organisms containing the following: autotrophs that produced organic compounds from CO2 either photosynthetically or by inorganic chemical reactions; heterotrophs that obtained organics by leakage from other organisms; saprotrophs that absorbed nutrients from decaying organisms; and phagotrophs that were sufficiently complex to envelop and digest prey." [italics added]. See--
* Kurland CG et al.(2006) Genomics and the irreducible nature of eukaryote cells. Science 312:1011-4 PMID 16709776

Other evidence suggests that “Extant life on Earth is descended not from one, but from three distinctly different cell types. However, the designs of the three have developed and matured, in a communal fashion, along with those of many other designs that along the way became extinct.” See--
* Woese CR (2002) On the evolution of cells. Proc Natl Acad Sci USA 99:8742-7 PMID 12077305.
53. ↑ Smolin L (1997) The Life of the Cosmos. New York: Oxford University Press. ISBN 019510837X
54. ↑ Varela FG, Maturana HR, Uribe R. (1974) Autopoiesis: the organization of living systems, its characterization and a model. Curr Mod Biol. 5:187-196 PMID 4407425
* "We assert that reproduction and evolution are not constitutive features of the living organization and that the properties of a unity cannot be accounted for only through accounting for the properties of its components. In contrast, we claim that the living organization can only be characterized unambiguously by specifying the network of interactions of components which constitute a living system as a whole, that is, as a "unity"."
* "We also claim that all biological phenomenology, including reproduction and evolution, is secondary to the establishment of this unitary organization."
* "Thus, instead of asking "What are the necessary properties of the components that make a living system possible?" we ask "What is the necessary and sufficient organization for a given system to be a living unity?""
* "In other words, instead of asking what makes a living system reproduce, we ask what is the organization reproduced when a living system gives origin to another living unity?"
55. ↑ Benner SA et al. (2004) Is there a common chemical model for life in the universe? Curr Opin Chem Biol 8:672-89. PMID 15556414
56. ↑ 56.0 56.1 Lehn JM. (2002) Toward complex matter: supramolecular chemistry and self-organization. Proc Natl Acad Sci USA 99:4763-4768 PMID 11929970
* From the article: Supramolecular chemistry has paved the way toward apprehending chemistry as an information science through the implementation of the concept of molecular information with the aim of gaining progressive control over the spatial (structural) and temporal (dynamic) features of matter and over its complexification through self-organization, the drive to life...Supramolecular chemistry has developed as the chemistry of the entities generated by intermolecular noncovalent interactions...
57. ↑ 57.0 57.1 Lehn JM (2002) Toward self-organization and complex matter Science 295:2400-3 PMID 11923524
58. ↑ Steed JW., Atwood JL. (2009) Supramolecular Chemistry. Wiley. ISBN 9780470512333. | Google Book preview. | Downloadable PDFs TOC & Chapter 1.
* Excerpt: If we regard supramolecular chemistry in its simplest sense as involving some kind of non-covalent binding or complexation event, we must immediately define what is doing the binding. In this context we generally consider a molecule (a 'host') binding another molecule (a 'guest') to produce a 'host-guest' complex or supermolecule. Commonly the host is a large molecule or aggregate such as an enzyme or synthetic cyclic compound possessing a sizeable, central hole or cavity. The guest may be a monatomic cation, a simple inorganic anion, an ion pair or a more sophisticated molecule such as a hormone, pheromone or neurotransmitter. More formally, the host is defined as the molecular entity possessing convergent binding sites (e.g. Lewis basic donor atoms, hydrogen bond donors, etc.). The guest possesses divergent binding sites [e.g. a spherical, Lewis acidic metal cation or hydrogen bond acceptor halide anion). In turn a binding site is defined as a region of the host or guest capable of taking part in a non-covalent interaction.
59. ↑ Percec V, Ungar G, Peterca M (2006) Self-assembly in action. Science 313:55-6 PMID 16825559
60. ↑ Reinhoudt DN, Crego-Calama M (2002) Synthesis beyond the molecule Science 295:2403-7 PMID 11923525
61. ↑ Lehn JM (2007) From supramolecular chemistry towards constitutional dynamic chemistry and adaptive chemistry. Chem Soc Rev 36:151-60 PMID 17264919
62. ↑ Hoelzer GA, Smith E, Pepper JW. (2006) Perspective: On the logical relationship between natural selection and self-organization. J Evol Biol. 19(6):1785-94.
63. ↑ Heylighen F (2001) The Science of Self-organization and Adaptivity. In: Kiel LD (ed.) Knowledge Management, Organizational Intelligence and Learning, and Complexity: The Encyclopedia of Life Support Systems EOLSS) Oxford: Eolss
* From the Abstract: Self-organization can be defined as the spontaneous creation of a globally coherent pattern out of local interactions…Formally, the basic mechanism underlying self-organization is the (often noise-driven) variation which explores different regions in the system’s state space until it enters an attractor. This precludes further variation outside the attractor, and thus restricts the freedom of the system’s components to behave independently. This is equivalent to the increase of coherence, or decrease of statistical entropy, that defines self-organization.
64. ↑ Harold FM. (2005) Molecules into cells: specifying spatial architecture. Microbiol Mol Biol Rev 69:544-64 PMID 16339735
* Abstract: A living cell is not an aggregate of molecules but an organized pattern, structured in space and in time. This article addresses some conceptual issues in the genesis of spatial architecture, including how molecules find their proper location in cell space, the origins of supramolecular order, the role of the genes, cell morphology, the continuity of cells, and the inheritance of order. The discussion is framed around a hierarchy of physiological processes that bridge the gap between nanometer-sized molecules and cells three to six orders of magnitude larger. Stepping stones include molecular self-organization, directional physiology, spatial markers, gradients, fields, and physical forces. The knowledge at hand leads to an unconventional interpretation of biological order. I have come to think of cells as self-organized systems composed of genetically specified elements plus heritable structures. The smallest self that can be fairly said to organize itself is the whole cell. If structure, form, and function are ever to be computed from data at a lower level, the starting point will be not the genome, but a spatially organized system of molecules. This conclusion invites us to reconsider our understanding of what genes do, what organisms are, and how living systems could have arisen on the early Earth.
65. ↑ 65.0 65.1 65.2 65.3 Loewenstein WR (1999) The Touchstone of Life: Molecular Information, Cell Communication, and the Foundations of Life. Oxford University Press, New York. ISBN 0-19-514057-5 Full-Text Online with Subscription
66. ↑ 66.0 66.1 Noble D (2002) Modeling the heart—from genes to cells to the whole organ. Science 295:1678-82]
67. ↑ Autobiography, Sidney Brenner, The Nobel Prize in Physiology or Medicine 2002.
68. ↑ Sidney Brenner’s Nobel lecture (2002) “Nature’s Gift to Science”
69. ↑ Brenner S (1998) Biological computation Novartis Found Symp 213:106-11 PMID 9653718
70. ↑ Dawkins R (1988) The Blind Watchmaker: Why the Evidence of Evolution Reveals a Universe Without Design. New York: W.W. Norton & Company, Inc. ISBN 0393304485.
* Excerpt from Amazon.com review: The title of this 1986 work, Dawkins's second book, refers to the Rev. William Paley's 1802 work, Natural Theology, which argued that, just as finding a watch would lead you to conclude that a watchmaker must exist, the complexity of living organisms proves that a Creator exists. Not so, says Dawkins: "the only watchmaker in nature is the blind forces of physics, albeit deployed in a very special way... it is the blind watchmaker." (Physics, of course, includes open-system non-equilibrium thermodynamics, pivotal to understanding how living systems fabricate and sustain themselves.)
71. ↑ Mendoza M et al. (2004) Emergence of community structure in terrestrial mammal-dominated ecosystems. J Theor Biol :203-214] PMID 15302552.
72. ↑ 72.0 72.1 72.2 72.3 Kauffman S. (2003) Molecular Autonomous Agents. Philosophical Transactions: Mathematical, Physical and Engineering Sciences 361:1089-1099.
73. ↑ Kauffman SA (2000) Investigations. Oxford University Press, Oxford. ISBN 019512104X Publisher’s description and reviews
74. ↑ Franklin S, Graesser A (1996) Is it an Agent, or just a Program?: A Taxonomy for Autonomous Agents. Proc Third Int Workshop on Agent Theories, Architectures, and Languages, Springer-Verlag
75. ↑ Kauffman S (2003) The Adjacent Possible
76. ↑ From: Bar-Joseph Z et al. (2003) Computational discovery of gene modules and regulatory networks. Nat Biotechnol 21:1337–42, available online at http://www.nature.com/nbt/journal/v21/n11/abs/nbt890.html. And: Qi Y, Ge H (2006) Modularity and dynamics of cellular networks. PLoS Comp Biol 2(12):e174. Available online at http://dx.doi.org/10.1371/journal.pcbi.0020174
77. ↑ 77.0 77.1 Barabási AL (2002) Linked: The New Science of Networks. Cambridge, Mass: Perseus Pub. ISBN 0-7382-0667-9
78. ↑ Watts DJ. (2007) A twenty-first century science. Nature 445:489
79. ↑ Alon U (2003) Biological networks: the tinkerer as an engineer. Science 301:1866-7 PMID 14512615
80. ↑ Hartwell LH, Hopfield JJ, Leibler S, Murray AW. (1999) From molecular to modular cell biology. Nature 402:C47-C52] PMID 10591225
81. ↑ Darwin C (1859) On the origin of species by means of natural selection, or the preservation of favoured races in the struggle for life. 1st edition. Chap. VI, p190 “Difficulties on Theory”

* Darwin wrote: “The illustration of the swimbladder in fishes is a good one, because it shows us clearly the highly important fact that an organ originally constructed for one purpose, namely flotation, may be converted into one for a wholly different purpose, namely respiration.”
* Stephen Jay Gould and others dispute Darwin on the direction of exaptation between swimbladder and lung, though not the rality of exaptation: Gould writes: “Darwin was wrong; ancestral vertebrates had lungs… The first vertebrates maintained a dual system for respiration: gills for extracting gases from seawater and lungs for gulping air at the surface. A few modern fishes, including the coelacanth, the African bichir Polypterus, and three genera of lungfishes, retained lungs… In two major lineages of derived bony fishes -- the chondrosteans and the teleosts -- lungs evolved to swim bladders by atrophy of vascular tissue to create a more or less empty sac and, in some cases, by loss of the connecting tube to the esophagus (called the trachea in humans and other creatures with lungs). See: Gould SJ (1993) Eight Little Piggies: Reflections in Natural History. Norton, New York. ISBN 039303416X.
82. ↑ See definition of ‘exapt’
83. ↑ Lenski RE et al. (2006) Balancing robustness and evolvability. PLoS Biol 4(12):e428]
84. ↑ 84.0 84.1 Alon U (2007) Simplicity in biology. Nature 446:497]
85. ↑ Prill RJ et al. (2004) Dynamic properties of network motifs contribute to biological network organization. PLoS Biol 3:e343]
86. ↑ Sporns O, Kotter R (2004) Motifs in brain networks. PLoS Biol 2:e369]
87. ↑ Alon U (2007) An Introduction to Systems Biology: Design Principles of Biological Circuits. Boca Raton: Chapman and Hall/CRC
88. ↑ Avery JS. (2012) Information theory and evolution. 2nd edition. Singapore: World Scientific, ISBN 9789814401234.
89. ↑ Brooks R. (2001) The relationship between matter and life. Nature 409:409-11.
90. ↑ Note: This article takes the view that a cell constitutes the unit ‘living systems’, and that cellular subsystems, like transcription networks and metabolic pathways, qualify as ‘biological systems’ but not as ‘living systems’.
91. ↑ Note: That does not explain how living systems came to acquire the ability to utilize available energy in the first place. To explain that requires knowledge of the origin of living systems. See Origin of life
92. ↑ Note: Usable energy, also called 'free energy', has all the attributes of information. Light, for example, can carry information as modulations of its frequency, amplitude, and phase. Photosynthesis-capable organisms harvest just the information needed for producing their own constituents in conjunction with their own stores of information relevant to that activity.
93. ↑ Richardson PJ, Boyd R (2006) Not By Genes Alone. The University of Chicago Press, Chicago. ISBN 0-226-71212-5
94. ↑ Nurse P. (2008) Life, logic and information. Nature 454:424–426.
95. ↑ Deacon TW (1997) The Symbolic Species: The Co-Evolution of Language and the Brain. New York: W.W. Norton & Company, Inc. ISBN 0393038386
96. ↑ Allman JM. (1999) Evolving Brains. New York: Scientific American Library. ISBN 0716750767. | Free PDF.
* See Chapter 1 for description of cognition in unicellular organisms.
97. ↑ Danchin A et al. (2007) The extant core bacterial proteome is an archive of the origin of life. Proteomics 7:875–89
98. ↑ Bray D. (2009) Wetware: A Computer in Every Living Cell. New Haven: Yale University Press. | Google Books preview | Review of book in Science: Marshall WF. (2009) What Is It Like to Be a Cell? Science 325:948.
* From publisher's description: Dennis Bray taps the findings of the new discipline of systems biology to show that the internal chemistry of living cells is a form of computation. Cells are built out of molecular circuits that perform logical operations, as electronic devices do, but with unique properties. Bray argues that the computational juice of cells provides the basis of all the distinctive properties of living systems: it allows organisms to embody in their internal structure an image of the world, and this accounts for their adaptability, responsiveness, and intelligence.
99. ↑ Hood L (2003) Systems biology: integrating technology, biology, and computation. Mechanisms of Ageing and Development 124:9-16]
100. ↑ 100.0 100.1 Maturana HR, Varela FJ. (1973) Autopoiesis: The Origin of the Living. In: Autopoiesis and Cognition: The Realization of the Living. D. Reidel Publishing Company, Dordrect:Holland. ISBN 90-277-1015-5
101. ↑ Hofmeyr JH (2007) "The biochemical factory that autonomously fabricates itself: A systems biological view of the living cell." In: Boogerd FC, Bruggeman FJ, Hofmeyr JH, and Westerhoff HV (editors). Systems Biology: Philosophical Foundations. Elsevier, Amsterdam. ISBN 13:978-0-444-52085-2 (see page 225)
102. ↑ Immanuel Kant. Kant’s Critique of Judgement, translated with Introduction and Notes by J.H. Bernard (2nd ed. revised) (London: Macmillan, 1914).
* Excerpt: For a body then which is to be judged in itself and its internal possibility as a natural purpose, it is requisite that its parts mutually depend upon each other both as to their form and their combination, and so produce a whole by their own causality; while conversely the concept of the whole may be regarded as its cause according to a principle (in a being possessing a causality according to concepts adequate to such a product).
* In this case then the connexion of effective causes may be judged as an effect through final causes.
* In such a product of nature every part not only exists by means of the other parts, but is thought as existing for the sake of the others and the whole, that is as an (organic) instrument.
* Thus, however, it might be an artificial instrument, and so might be represented only as a purpose that is possible in general; but also its parts are all organs reciprocally producing each other.
* This can never be the case with artificial instruments, but only with nature which supplies all the material for instruments (even for those of art). Only a product of such a kind can be called a natural purpose, and this because it is an organised and self-organising being. [Excerpt bulleted for ease of reading]
103. ↑ Alexander J. (1948) Life: Its Nature and Origin New York: Reinhold Pub. Corp.
104. ↑ Harold FM (2003) The Way of the Cell: Molecules, Organisms, and the Order of Life New York: Oxford University Press. p220.
105. ↑ Varela F. (2001) The Emergent Self. In: The Third Culture, by John Brockman. Chapter 12.
106. ↑ 106.0 106.1 Bitbol M, Luisi PL (2004) Autopoiesis with or without cognition: defining life at its edge. PMID 16849156
107. ↑ Varela FG, Maturana HR, Uribe R (1974) Autopoiesis: the organization of living systems, its characterization and a model. Curr Mod Biol 5:187-96 PMID 4407425
* We assert that reproduction and evolution are not constitutive features of the living organization and that the properties of a unity cannot be accounted for only through accounting for the properties of its components. In contrast, we claim that the living organization can only be characterized unambiguously by specifying the network of interactions of components which constitute a living system as a whole, that is, as a "unity".
* We also claim that all biological phenomenology, including reproduction and evolution, is secondary to the establishment of this unitary organization.
* Thus, instead of asking "What are the necessary properties of the components that make a living system possible?" we ask "What is the necessary and sufficient organization for a given system to be a living unity?" In other words, instead of asking what makes a living system reproduce, we ask what is the organization reproduced when a living system gives origin to another living unity?
108. ↑ Note: Taking homeostasis to mean stability of self-construction and self-sustenance, a living machine might achieve that by incorporating the perturbation (e.g., a foreign molecule) into its organization.
109. ↑ Hayden EC. (2010) Human genome at ten: Life is complicated. & See quote by Leonid Kruglyak.
110. ↑ Andrea Falcon (2006) Aristotle on Causality
111. ↑ Bothwell JHF. (2006) The long past of systems biology. (Free Full-Text). New Phytologist 170:6-10.
112. ↑ Note: We might interpret Aristotle's four components of 'causality' as four components of 'explanation', for as Bothwell writes: "Aristotle (384-322 BCE) wanted to search for explanations of natural events that inspire wonder. His search led him to conclude that any question which might be asked about the behaviour of a complex, apparently designed, system might be answered if we knew four properties of that system. He called these the aitiai, a word which is usually rendered into English as 'causes', but which may be better translated as 'explanations'.
113. ↑ Bhalla US, Iyengar R (1999) Emergent properties of networks of biological signaling pathways. Science 283:381-7 PMID 9888852 Link-1 Link-2
114. ↑ Luisi PL. (2002) Emergence in Chemistry: Chemistry as the Embodiment of Emergence. Foundations of Chemistry 4:183-200.
115. ↑ Jablonka E, Lamb MJ (2005) Evolution in Four Dimension: Genetic, Epigenetic, Behavioral, and Symbolic Variation in the History of Life. Cambridge: MIT Press.
116. ↑ Gorelick R (2004) Neo-Lamarckian medicine. Med Hypotheses 62:299-303 PMID 14962644.
* Abstract: Darwinian medicine is the treatment of disease based on evolution. The underlying assumption of Darwinian medicine is that traits are coded by genes, which are often assumed to be sequences of DNA nucleotides. The quantitative genetic ramification of this perspective is that traits, including disease susceptibility, are either caused by genes or by the environment, with genotype-by-environment interactions usually considered statistical artefacts. I emphasize also examining those epigenetic signals that can be altered by environmental perturbations and then transmitted to subsequent generations. Although seldom studied, environmentally-alterable meiotically-heritable epigenetic signals exist and provide a mechanism underlying genotype-by-environment interactions. Environment of a parent can affect its descendants by heritably altering epigenetic signals. Neo-Lamarckian medicine is the application of these evolutionary epigenetic notions to diseases and could have enormous public health and environmental policy implications. If industrial contaminants adversely affect organisms by meiotically-heritably altering their epigenetic signals, then cleaning up these contaminants will not remedy the problem. Once contaminants have adversely altered an individual's epigenetic signals, this harm will be transmitted to future generations even if they are not exposed to the contaminant. Exposure to environmental shocks such as free radicals or other carcinogens can alter cytosine methylation patterns on regulatory genes. This can cause cancer by up-regulating genes for cell division or by down-regulating tumour suppressor genes. Environmentally-alterable meiotically-heritable epigenetic signals could also underlie other diseases, such as diabetes, Prader-Willi syndrome, and many complex diseases. If environmentally-altered meiotically-heritable epigenetic effects are widespread - which is an important open empirical question - they have the potential to alter paradigmatic views of evolutionary medicine and the putative dichotomy of nature versus nurture. Neo-Lamarckian medicine would thereby shift emphasis from cure to prevention of diseases.
117. ↑ 117.0 117.1 Gilbert SF, Sarkar S. (2000) Embracing Compleity: Organicism for the 21st Century. Developmental Dynamics 210:1-9.
118. ↑ Walsh DM (2006) Organisms as natural purposes: the contemporary evolutionary perspective. Stud Hist Philos Biol Biomed Sci 37:771-91]
119. ↑ 119.0 119.1 Committee on Defining and Advancing the Conceptual Basis of Biological Sciences in the 21st Century, National Research Council. (2008) The Role of Theory in Advancing 21st Century Biology: Catalyzing Transformative Research. Board on Life Sciences, Division on Earth and Life Studies, National Research Council of the National Academies. The National Academies Press, Washington, D.C. ISBN 978-0-309-11249-9.
120. ↑ Tabony J (2006) Microtubules viewed as molecular ant colonies. (Free Full-Text) Biol Cell 98:603-17 PMID 16968217.

* Abstract: Populations of ants and other social insects self-organize and develop ‘emergent’ properties through stigmergy in which individual ants communicate with one another via chemical trails of pheromones that attract or repulse other ants. In this way, sophisticated properties and functions develop. Under appropriate conditions, in vitro microtubule preparations, initially comprised of only tubulin and GTP, behave in a similar manner. They self-organize and develop other higher-level emergent phenomena by a process where individual microtubules are coupled together by the chemical trails they produce by their own reactive growing and shrinking. This behaviour is described and compared with the behaviour of ant colonies. Viewing microtubules as populations of molecular ants may provide new insights as to how the cytoskeleton may spontaneously develop high-level functions. It is plausible that such processes occur during the early stages of embryogenesis and in cells.
121. ↑ Theise ND, d'Inverno M. (2004) Understanding cell lineages as complex adaptive systems. Blood Cells Mol Dis 32:17-20 PMID 14757407.

* Abstract: Stem cells may be considered complex reactive systems because of their vast number in a living system, their reactive nature, and the influence of local environmental factors (such as the state of neighboring cells, tissue matrix, stem cell physiological processes) on their behavior. In such systems, emergent global behavior arises through the multitude of local interactions among the cell agents. Approaching hematopoietic and other stem cell lineages from this perspective have critical ramifications on current thinking relating to the plasticity of these lineage ystems, the modeling of stem cell systems, and the interpretation of clinical data regarding many diseases within such models.
122. ↑ Ruiz i Altaba A et al. (2003) The emergent design of the neural tube: prepattern, SHH morphogen and GLI code. Curr Opin Genet Dev 13:513-21 PMID 14550418.
123. ↑ Jeong H et al.(2000) The large scale organisation of metabolic networks. Nature 407:651-4]
124. ↑ e.g. Grindrod P, Kibble M (2004) Review of uses of network and graph theory concepts within proteomics. Expert Rev Proteomics 1:229-38 PMID 15966817
125. ↑ Ye X et al.(2005) Multi-scale methodology: a key to deciphering systems biology. Front Biosci 10:961-5 PMID 15569634
126. ↑ Cho YS et al. (2005) Self-organization of bidisperse colloids in water droplets. J Am Chem Soc 127:15968-75 PMID 16277541
127. ↑ see e.g. Burak Y, Fiete I (2006) Do we understand the emergent dynamics of grid cell activity? J Neurosci 26:9352-4 PMID 16977716
128. ↑ e.g. Courtney SM (2004) Attention and cognitive control as emergent properties of information representation in working memory. Cogn Affect Behav Neurosci 4:501-16 PMID 15849893
129. ↑ Theraulaz G et al (2002) Spatial patterns in ant colonies. Proc Natl Acad Sci USA 99:9645-9 PMID 12114538
130. ↑ Theraulaz G, Bonabeau E (1999) A brief history of stigmergy. Artif Life 5:97-116 PMID 10633572
131. ↑ Bonabeau E, Meyer C (2001) Swarm intelligence. A whole new way to think about business. Harv Bus Rev 79:106-14 Download PDF of article PMID 11345907
132. ↑ Kauffman S. (2001) Prolegomenon to a General Biology.
* Excerpt:…no one designed and built the biosphere. The biosphere got itself constructed by the emergence and persistent coevolution of autonomous agents…I suspect that biospheres maximize the average secular construction of the diversity of autonomous agents and the ways those agents can make a living to propagate further. In other words, on average, biospheres persistently increase the diversity of what can happen next. In effect… biospheres may maximize the average sustained growth of their own “dimensionality.”
133. ↑ (1991) Zurek WJ (ed) Complexity, Entropy, and the Physics of Information: The Proceedings of the Workshop on the Complexity, Entropy, and the Physics of Information May-June, 1989, Santa Fe, New Mexico. Addison-Wesley Publishing Company, The Advanced Book Program, Redwood City. Book preview by Google Books -ISBN 0201515091
134. ↑ Hazen RM (2005) Genesis: The Scientific Quest for Life's Origin. Joseph Henry Press, Washington DC. | Book description, reviews, and for-fee downloadable PDF of entire book or individual chapters | ISBN 0309094321.
135. ↑ Note: We can arrive at a more-or-less empirically sound explanation of what constitutes living systems without having a good explanation for how they arose in the first place; we can study the here-and-now and not the there-and-then;
136. ↑ Odling-Smee FJ, Laland KN, Feldman MW (2003) Niche Construction; The Neglected Process in Evolution. Princeton: Princeton University Press. ISBN 0691044384. | Google Books extensive excerpts. | Website with bibliography on niche construction. | [http://www.nicheconstruction.com/ Niche Construction: The Neglected Process in Evolution. Authors' website, including sample chapter of book].
137. ↑ 137.0 137.1 Damasio A. (2003) Looking for Spinoza: Joy, Sorrow, and the Feeling Brain. Orlando, Florida: Harcourt, Inc. Book synopsis. | Google Books preview. | ISBN 978-0099421832, ISBN 978-0151005574
138. ↑ Stewart I. (2011) The Mathematics of Life. Basic Books. Kindle edition.

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