Life/Citable Version

Biologists use the term life to refer to the processes comprising the activity of living, to the entities that embody those processes, and to the interrelations and interactions among those entities — complex adaptive systems. The question turns on what precisely characterizes the 'processes of living'. In answering that, biologists hope to find answers to many other questions in biology, perhaps even some not yet asked (see Biology and Systems biology).

This article will provide a fundamental structure enabling the reader to learn heuristically what constitutes 'living'. Until understanding emerges full-blown, the reader must, so to speak, live with the word in the contexts in which it exists during the unfolding of this article.

Spotted wildlife: (a) whale shark (Rhincodon typus – Photo © G. Taylor); (b) spotted tree frog (Hyla leucophyllata – Photo © D. Bickford); (c) northern quoll, (Dasyurus hallucatus – Photo © J. Kirwan); (d) Amazon spotted frog (Hyla punctata – Photo © D. Bickford); (e) striped blue crow (Euploea mulciber – Photo © D. Lohman); and (f) mangrove snake (Boiga dendrophilia – Photo © D. Bickford). From: Speed CW, Meekan MG, Bradshaw CJA (2007) Spot the match – wildlife photo-identification using information theory. Frontiers in Zoology 4:2 doi:10.1186/1742-9994-4-2. http://www.frontiersinzoology.com/content/4/1/2.

Linguistic Considerations Relating to the Definition of Life

Ernst Mayr, a 20th century giant among evolutionary biologists, in his last decade as a centenarian, wrote a book called This is Biology: The Science of the Living World. In the opening chapter, What Is the Meaning of “Life” (his quotation marks), he declares that understanding 'life' is one of the major objectives of biology. However, he suggests that we should fuss less about defining 'life', and concentrate more on defining the process of 'living':

Evolutionary biologist Ernst Mayr (1904-2005) in 1994. Author of: Mayr E (2005) This is Biology: The Science of the Living World. Cambridge, Mass: Belknap Press of Harvard University Press. ISBN 067488468X. See encomium: Meyer A (2005) On the importance of being Ernst Mayr. PLoS Biol 3(5): e152

"The problem here is that "life" suggests some "thing"—a substance or force—and for centuries philosophers and biologists have tried to identify this life substance or vital force, to no avail. In reality, the noun "life" is merely a reification of the process of living (emphasis added). It does not exist as an independent entity. One can deal with the process of living scientifically, something one cannot do with the abstraction "life". One can describe, even attempt to define, what living is; one can define what a living organism is; and one can attempt to make a demarcation between living and nonliving. Indeed, one can even attempt to explain how living, as a process can be the product of molecules that themselves are not living." (Mayr 1997, page 2).

Scientist Eric Schneider and science writer Dorian Sagan echo Mayr:

"...the word is a grammatical misnomer: life is a noun, but the phenomenon to which it refers is a process. And it is vitalistic: when we say life, we think we know what we are talking about when often we have simply applied a label that allows us to categorize, rather than examine closely, the phenomenon about which we are speaking."

Ultimately, all definitions of words in terms of other words converge on about 70 so-called "semantic primes" (words that cannot be defined in terms of other words, which are universal among languages, and the meaning of which children learn by the way they are used in the society in which they live). Every other word can be defined using some combination of semantic primes. The verb “live” is one of these semantic primes. Using semantic primes, 'Life' is defined as 'that which lives', where lives is understood by speakers and listeners from their experience with the language-speakers in their environment; they also know primitively that things which live 'die' and generate the word 'death' to refer to 'that which died'.

The question, then, not “what is life?”, but “what characterizes things that live?” Biologists act on the latter question, even as they ask it in terms of the former. The biologist, logician and historian J.H. Woodger suggested that the word "life" can be eliminated from the scientific vocabulary, because it is "an indefinable abstraction and we can get along perfectly well with "living organism" which is an entity which can be speculatively demonstrated.” Carol Cleland, philosopher and member of NASA’s Astrobiology Institute, adds that scientists are not really interested in what the word "life" happens to mean in our language. "What we really need to focus on is coming up with an adequately general theory of living systems, as opposed to a definition of "life."" Perhaps this resonates with the remark of biologist Antonio Lazcano: "Life is like music; you can describe it but not define it". ).

Differing Perspectives on What Constitutes a Living System

As well as sharing a common carbon- and water-based chemistry, entities that biologists generally acknowledge as living — bacteria, trees, fish, chimpanzees etc. — share a common basic building block, the cell. The cell is the smallest system thought capable of independent living. Many organisms live as single cells, some are cooperative colonies of single cells, others are complex multicellular systems, with many different cell types specialized for different functions. Nature has produced an enormous variety of cell types in three vast ‘domains’ of living systems: Archaea, Bacteria, and Eukarya, yet all three domains share the cellular feature of compartmentalization from their environment by a surrounding lipid-protein membrane, the plasma membrane. Moreover, the cells in all three domains are ‘manufactured’ by pre-existing cells. All extract chemical energy from simple sugar molecules’ chemical bonds, converting it by chemical reactions into energy forms for many different purposes, ultimately enabling them to respond to their evolutionary imperative of self-reproduction. They all possess a molecular (i.e., DNA) embodied code, using essentially the same ‘genetic code’ that guides the production of the many different proteins that give structure and function to the cells. All replicate their DNA faithfully or nearly so, and thereby have the capacity to replicate themselves.

From those basic shared characteristics, biologists view the commonalities and uniquenesses of cell types, and living systems in general, from differing perspectives, all of which contribute to understanding what constitutes 'living'.

Systems

(See main article, Systems biology)

The 'systems perspective' recalls Aristotle's four components of an explanation for a complex natural living system:

• the list of organic and inorganic parts (e.g., carbon-containing molecules and inorganic ions; cells; organs; organisms) — Aristotle’s 'material' explanation;
• how the parts relate to each other to form substructures (e.g. networks) and how they interact with each other (e.g. network dynamics), and how the substructures interact among themselves in a coordinated dynamic, and hierarchical manner (e.g. cellular patterns of static and dynamic form) — Aristotle’s 'formal' (form-like) explanation];
• how the parts and substructures became so organized (e.g. gene expression; self-organization; competition) — Aristotle’s 'efficient' (effect-producing) explanation; and,
• how the living system as-a-whole functions and behaves and the properties that characterize it (e.g. reproduction; locomotion) — Aristotle’s 'final' explanation.

The analysis of those different components together now have formalized into an academic discipline, "Systems Biology", and they apply not just to cells but to all living systems. Systems biologists study, among other things, the phenomenon of ‘emergence’ in living systems, whereby properties, functions and behaviors of living systems arise not shared by any of its constituent components and not predictable from a reductionist characterization of the components isolated from the system embedding them. All cell and cellular systems exhibit such novel, or ‘emergent’, properties, functions and behaviors. The inability to predict these properties from the properties of its constituent components needs explanation, as such predictions have characterized the reductionist paradigm. There are two related reasons for that constraint on prediction:

• the intrinsic properties, functions and behaviors of the components do not determine those of the whole system. Rather, their organizational dynamics within the system does, where 'organizational dynamics' includes the interrelations of the components and their dynamic, coordinated, hierarchical interactions;
• the system-as-a-whole operates in its own context (its external environment) which affects the properties, functions and behaviors of the system-as-a-whole. The results of that contextual impact in turn affect the organization of the system's components — a 'downward causation'.

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’." In other words, the organization of the system's components determine its behavior, but that organization does not arise solely because of the intrinsic properties and behaviors of the components. The system's behavior, as it interacts with its environment, influences the organization of its components, and novel behaviors of the system 'emerge' that are not predictable from the intrinsic properties, functions and behaviors of the components alone. For example, the behavior of a kidney cell depends not only on the intrinsic characteristics of its components, but also on the organ (kidney) which constitutes its environment, because that environment influences the cell’s structure and behavior, which in turn influence the organization of the components.

Systems biologists refer to those two determinants of a system's behavior as 'bottom-up' and 'top-down' effects. The novel emergent properties, functions and behaviors that result from a combination of bottom-up and top-down effects constitute general characteristics of living systems.

Thermodynamic

Biologists sometimes view living things from the perspective of thermodynamics—the science of interactions among energy (capacity to do work), heat (thermal energy), work (movement through force), entropy (degree of disorder) and information (degree of order). The interactions define what the system can and cannot do in the process of interconverting energy and work. For example, by the First Law of thermodynamics, when a process converts one form of energy to another, it results in no net loss of energy, and no net gain.

Appreciation of the insight the thermodynamic perspective gives to explaining what constitutes a living entity requires an understanding of the laws of thermodynamics that scientists discovered through experiment, debate, mathematical formulation and refinement, and that Albert Einstein believed stood as an edifice of physical theory that could never topple. Most pertinent, the Second Law of Thermodynamics, has several expressions:

• Heat flows spontaneously — i.e., without external help — from a region or body of higher temperature to one of lower temperature, and never flows spontaneously in the reverse direction. That also holds for other forms of energy (e.g. electromagnetic, chemical, etc.) — concentrations of energy disperse themselves to lower energy levels, flowing “into the cool”, so to speak.
• When heat as input to a system causes the system to perform work (e.g. a steam engine), part of the heat disperses as ‘exhaust’, unused and unusable by the system for further work. That holds as well for other forms of energy doing work. Some of the energy always turns into ‘exhaust’, typically heat. Energy conversion to work in a system can never proceed at 100% efficiency—an empirical fact.
• The degree of order or organization of a system and its surroundings cannot spontaneously increase; it either remains the same or decreases. Scientists have learned to put a number on the degree of disorder of a system, and they refer to it as 'entropy'. Water vapor, with its water molecules in more or less random distribution, has a higher entropy than liquid water, with its molecules distributed less randomly, and has a higher entropy than ice, with its molecules distributed in a more organized crystal array. Left to itself, 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.

Those three expressions of the Second Law in effect restate each other as tenets of classical thermodynamics reflecting the empirical fact that high energy and order spontaneously flow downhill — down a ‘gradient’ — toward eliminating the gradient, as if nature abhors gradients of energy and order. Upon gradient elimination, all energy and order has degraded, all tendencies to change disappear, no further change occurs, and an equilibrium state ensues.

Given the universality of the Second Law, how do living entities manage to come into existence, to develop from an ‘embryonic’ state to one of greater order and lesser entropy, and to perpetuate their order and increase in order? How do they thwart the Second Law?

They don’t. They only appear to do it. Actually, they exploit the Universe’s gradients of energy and order — which run 'downhill' — by their location along those gradients, between the energy input and exhaust. Like a steam engine, they ‘import’ energy and order, converting it to the work of internal organization, reducing their entropy. 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 increase — in keeping with the Second Law.

Science has formalized that concept in the field of 'non-equilibrium' thermodynamics. It describes many of the characteristics of living systems that remain (for a lifespan) in a steady-state of organized functional activity. A living system performs its organized functional activities far from the 'equilibrium' state of activity of the system that would obtain if it did not have access to and ability to store and use available energy (including mass-energy) from outside the system. Such systems can store energy and perform work on themselves and outside; the available outside energy supplies the driving force that keeps the system functioning far-from-equilibrium and in disequilibrium with its environment. Systems maintained far-from-equilibrium can exhibit unexpected behaviors like chaos and self-organization.

Biological cells qualify as non-equilibrium thermodynamic systems because they must consume energy to live, and because they reach an equilibrium state only in death, whereupon all parts relate to each other according to spontaneous physicochemical processes. Viewing living systems from this perspective gives biologists mathematical tools to work with to learn how the system organizes itself. Those tools may help find ways to eliminate accumulated dysfunctions in the organizational activity of a living system that eventually causes it fail to maintain its optimal organization sufficiently to keep the system organized and therefore far-from-equilibrium. Slowing or eliminating dysfunctions of organizational activities might increase lifespan.

We can, then, view a living system as a state of organizational activity (non-randomness) that is maintained by importing, storing and transforming energy and matter from its external environment into the work and structures needed to sustain its organizational activity. In doing so, living systems produce waste and export it to the external environment, lowering the organizational state of the environment. The living system thus maintains its internal organization at the expense of the external environment, leaving the environment more disorganized than the gain in organization of the living system — in keeping with the second law of thermodynamics that the total disorder (system plus environment) always increases.

Thus, from a thermodynamic perspective, the following could serve as a fundamental characterization of a living system:

• The ability to remain for a time (a 'lifespan') as an organized, coordinated functioning system, in which spontaneous tendencies and external forces that tend to disturb its organization are opposed by built-in self-correcting mechanisms fueled by external resources (energy, matter) and facilitated by production and exportation of waste (disorder) — thus operating far from an ever-approaching equilibrium (the state that we call 'death').

That characterization needs elaboration as we consider other important perspectives on what constitutes a living entity.

Evolutionary

The thermodynamic characterization might also apply to some non-living systems such as a tornado or the flame of a candle. However, tornados and candle flames cannot 'reproduce' themselves, as cells and organisms do. One might then characterize living systems as also having: the capability in principle of reproducing themselves before equilibrium arrives. When a living system reproduces itself, random events (including 'mutations') introduce variations in the system's properties. Some variations offer some progeny, or the progeny of some conspecific living systems, less opportunity to reproduce than others, and other progeny better opportunity, sometimes better even than their progenitors, given either changes in environmental conditions or limitations of environmental resources. Accordingly, new groups with different properties arise, and may supplant older groups by out-competing them for resources. Biologists call that process 'evolution by means of natural selection', and regard it as the most important way, though not the only one, whereby living systems evolve over geological time..

Therefore, an important characteristic of living systems is descent with modification: the ability to produce offspring that inherit some of its features, but with some variation due to chance. Evolution by means of natural selection will occur if heritable variations in the offspring result in differential reproductive fitness. The variations occur due to chance variations in the inherited genetic recipe (genotype) for constructing the offspring's phenotype. In all biological systems, DNA or the related molecule, RNA, primarily provides the genetic recipe.

Viruses have few of the characteristics of living systems described above, 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.

Enlarging the description, we can say that living systems have:

• The ability to remain (for a "lifespan") as a compartmentalized, organized, coordinated functioning system, in which spontaneous and externally forced tendencies to disorganization meet offsetting built-in self-correcting mechanisms fueled by external resources (energy, matter) and facilitated by production and exportation of waste (disorder), thus all the while operating far from an ever-approaching equilibrium (aka death), and capable in principle of reproducing themselves before equilibrium arrives, and of evolving over historical time to adapt to environmental conditions.

Thus, living systems extract environmental resources and export waste (disorder) to produce functional organization with the ability to do work, reproduce with variation, and evolve transgenerationally by natural selection.

Exobiological

Exobiologists (also known as "astrobiologists") concern themselves with issues relating to the possible existence of extraterrestrial living systems. Dirk Schulze-Makuch and Louis Irwin attempted to distill the essential characteristics of a living system. They stress these characteristics, which resonate with the systems, thermodynamic and evolutionary perspectives discussed above:

• a microenvironment with a boundary between it and its external environment,
• the capability of that microenvironment to transform energy and matter from the environment to maintain a low entropy state (i.e., highly ordered or organizational state),

• therefore, the capability of that microenvironment to remain in thermodynamic disequilibrium with its environment,

• the capability of that microenvironment to encode and transmit information.

Self-Organization

Living systems organize themselves spontaneously. Molecular self-organization in cells emerges in part from the chemical properties of the proteins encoded in genes. Those proteins make their appearance through a genetic transcription-translation machinery, which represents a self-organized molecular machine emerging in part from the chemical properties of proteins and other molecules. Molecules interact through the formation and breaking of strong covalent bonds and also through weaker, quasi-stable non-covalent electromagnetic interactions, like hydrogen bonding and van der Waals forces and many others. Those weaker ‘supramolecular’ interactions give physical properties to molecular aggregates, and allow many intracellular and intercellular biological processes.

The qualifier, ‘in part’, in the preceding paragraph reflects the need to invoke not only molecular self-assembly but also evolutionary mechanisms selecting genes that yield proteins whose chemical properties enable interactions that tend to optimize functional self-organization—in other words, adaption to circumstances. One must also invoke local real-time selective processes that confer stability and appropriate functionality to molecular self-assembly. Self-organization and adaptation conjoin to yield function.

One way to appreciate self-organization of cell structure and function is to view the genome metaphorically as a computer, in which the genome functions as a ‘program’ that constructs critical components of the cell that can arrange themselves in a way that accords with their chemical properties. That arrangement, with the tinkering comprising local trial-and-error and evolution’s handiwork, can then carry out ('compute') integrative functions not explicitly encoded in the genome.

As Oxford professor Denis Noble reminds us, the Nobel Prize-winning molecular biologist Sidney Brenner expressed the 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.”

The patterns of structure and behavior in self-organized systems need no behind-the-scene master, and no prepared recipes that explicitly specify the organizational structure and dynamics of the system, instead, they emerge from the interactions among the components dictated by their physical properties as dynamically modified by consequences of the emerging organization embedded in its environment.

The single-celled zygote self-organizes into a multicellular living system as the properties of the genetically encoded proteins interact in accord with their physical properties, responding to changing influences stemming from the changing environment generated by growing multicellularity—self-organizing into a network of multiple cell-types doing cooperative work.

Self-organization tends to breed greater degrees of self-organization — breeding more complexity. Genes express not only proteins that organize themselves into a functional unit but also proteins that organize themselves to regulate that functional unit, as in transcription regulatory circuits. Protein networks interact in a self-organizing way to produce networks of networks with complex levels of coordination. Cells communicate with other cells, either in free-living cellular communities or in multicellular organisms—communicative activities that self-organize in virtue of the properties, functions and behaviors of the cells, selected for fitness by evolutionary mechanisms, and responsive to downward regulation by environmental influences on the whole system.

Autonomous Agents

Stuart Kauffman emphasizes the concept of ‘autonomous agents’ in explaining living systems. 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'. It requires energy to produce an excess of the enzyme from its subcomponents, beyond its equilibrium concentration. This comes from the release of the energy in an energy-rich bond of another molecule in the vicinity. The energy comes from breaking apart an energy-rich bond connecting that energy-rich molecule's subunits. The neighbor molecule serves as a motor to produce excess enzyme. The self-replication stops after using all duplicates of the motor, so to sustain self-replication, external energy—perhaps coming from light impinging on the system—must drive the repair of the broken chemical bond, re-establishing an ample supply of that energy-supplying energy-rich molecule, thereby re-energizing the motor. A new cycle of 'auto-catalytic self-replication' can then begin, given an ample influx of the sub-components of the 'auto-catalytic' enzyme and of energy—food and energy. As an essential feature, within the system, interactions (couplings) among its components have effects (technically ‘allosteric’ effects) that help ‘organize’ and ‘coordinate’ the system’s processes, allowing the autonomously self-replication to flow.

Kauffman conceives, then, of a self-replicating autocatalytic molecule in a network of molecules that has repeat cycles of self-replication driven by external energy and materials. The network has a self-replication process as a subsystem, and a ‘motor’, namely, the breakup of an energy-rich molecule’s chemical bond, supplying energy that 'drives' the auto-catalysis self-replication, and its re-energizing repair by transduction of the outside energy source. Kauffman calls such a network a ‘molecular autonomous agent’ because, given a source of external energy (e.g. photons) and ample materials (the molecules needed to assemble the autocatalytic enzyme), the network perpetuates its existence autonomously, i.e., not controlled by outside forces even though dependent on outside energy and materials. The ‘agent’ is the system doing work autonomously, in this case the work of auto-catalytic self-replication. That's what 'agents' do — they do work.

In the above case, the agent acts in its own behalf—continuing its existence by ‘eating’ outside materials and energy. Work gets done because the system remains far-from-equilibrium, with influxing excess outside energy and materials. Energy flows through the system, doing work, and the system can only do work when those far-from-equilibrium conditions persist. At equilibrium, no work gets done because no energy flows through the system. Thus the agent continues 'to live' (survive and self-replicate) only while that far-from-equilibrium state exists, and it can be starved to ‘death’ by removing the matter and energy flowing through the system. Kauffman argues, from his example, that cells, and indeed all living systems, qualify as autonomous agents, constructed on a foundation of molecular autonomous agents.

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 Kauffman's 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.

For Kauffman, the property of pursuing its own agenda includes acting as a naturally selected system contributing to its own survival and self-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.”

Networks

The science of networks provides another perspective on the nature of living things. Networks ‘re-present’ a system, or subsystem, as a collection of ‘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 some kind and return outputs of a different kind.

One ‘finds’ networks everywhere in biology, from intracellular molecular networks, to intraspecies networks, to ecosystem networks: gene regulatory circuits, social groups of chimpanzees, entangled banks. Humans deliberately construct networks, of individuals working to a common purpose (e.g. the U.S Congress), of electronic parts to produce desired outputs (e.g. mobile phones), of sentences and paragraphs to express messages (e.g. this article). Researchers view the World Wide Web as a network and study its characteristics and dynamics. Referring to cells, Alon says: “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.”

Alon notes that cellular networks resemble many types of human engineered networks, in that they show what network analysts call ‘modularity’, ‘robustness’, and ‘motifs’.

• Modules comprise subnetworks that perform a specific function and that connect with other modules only at one input node and one output node. Modularity offers ease of cellular adaptation to changing environments, as, to produce the adaptation, evolution need tinker with just a single or a few modules rather than with the whole system. Evolution can exapt existing modules for novel functions that contribute to survival.
• Robustness offers continued functionality of a network in the face of typical deviations in the state of the components due to environmental perturbations. Robustness restricts the range of network types researchers have to consider because only certain types enable robustness.
• Network motifs offer economy of design, as the same circuit design can have widespread applicability in cellular regulation, as in the case of autoregulatory circuits and feedforward loops (see cell). Networks, like those in cells and those in neural networks in the brain, employ motifs as basic building blocks, like multicellular organisms employ cells as basic building blocks.

The view of the cell as an overlay of mathematically-definable dynamic networks, especially when analyzed in detail in relation to known cellular activities, can reveal how a living system can exist as an improbable intricate self-orchestrated dance of molecules. It also suggests how the concept of self-organized networks can extend to all higher levels of living systems.

Self-organized networks, but not randomly self-organized. Natural selection favors self-organized networks that contribute to the reproductive fitness of the system, as they coordinate with the other self-organized networks in the system.

Information Processing

Bioscientists study biological systems for many different reasons, hence biology has many subdisciplines (see Biology and List of biology topics). But whatever the subdiscipline, bioscientists study biological systems for the proximate reason of gaining information about the system (satisfying curiosity), and to apply that information to human agendas (e.g. disease prevention, environmental conservation). Those realities attest that biological systems harbor information, at least as humans commonly view information. To appreciate how viewing biological systems from an ‘information’ perspective can contribute to understanding what constitutes a living system, 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 in something, to give it form. 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, inasmuch as the second law of thermodynamics teaches us that the universe, and any other 'isolated' system, tends to randomness as its most probable state. 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 in smithereens.

The more improbable the arrangements, the more in-formation a collection of parts has received and therefore contains. A monitor of the collection over time has a degree of certainty 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.

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 in the arrangement. Biological systems thus have information content, in that they are unlikely (non-random) arrangement of parts, non-random collections of interactions of parts, non-random collections of functional activities.

The thermodynamic and autonomous agent perspectives on living systems discussed the notion of cells as intermediates in a gradient of higher to lower forms of usable energy, including mass-energy. The flow of energy and materials through the living system feeds it, enabling it to do work on itself. That work enables it to give itself form, or order, and to give itself functionalities, raising its information content. The cell can do work on its environment also.

Thus a living system emerges as an information processing system. It can:

• receive information from energy and materials in its environment, fueling and supplying the machinery that builds and sustains information-rich organization;
• generate new information inside itself, as in embryonic development;
• transmit information within and outside itself, as in transcription regulation and exporting pheromones.

From its parent, it inherits information establishing its developmental potential and scripting its realization, including controlling what parts of the inherited information-base transmit their piece of information within or outside, depending on cell-type and environmental conditions — and including information that enables it to reproduce itself.

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

A Synthesis of Perspectives

In regard to the question of what constitutes a living system, what do the several perspectives discussed above, together, offer in answer, if anything? They seem to involve a few basic concepts:

• living systems can import work-enabling energy, matter, and information directly or indirectly from the Universe in earth’s vicinity, the ultimate source possibly the singularity that exploded in a "big bang" 13.7 billion years ago;

• they also can export to their environment unusable and information — poor energy and matter;

• those two abilities enable them to delay (for a lifetime) the ultimate dictate of the second law of thermodynamics, which moves organized systems to the more probable disorganized state of the equilibrium of randomness;

• they also can self-organize and self-maintain their fully-functioning living system, given the availability of basic information that generates their critical structural components

• that information comes as part of the starting materials in the basic building blocks of all living systems, namely cells;

• cells inherit information from ‘parent’ cells — unique to living systems — raising two questions that no perspective on what constitutes a living cell addresses, namely how did cells arise in the first place and how did they acquire information banks?;

• that information, in the form of nucleic acid macromolecules, encode many different types of amino acid macromolecules, that, once produced, interact by strong and weak molecular encounters among themselves and with their encoding macromolecules, in the process self-assembling an organization that sustains its ability to import work-enabling energy, matter, and information directly or indirectly from the local Universe;

• that self-organizing activity occurs without a master controller other than that of physicochemical laws, but needs a type of activity that supports the system far-from-equilibrium, which can yield improbable self-organized structures and activities;

• the physicochemical laws, at the most general level, include:

• the laws that allow local energy importation and the accumulation of order, organization and information by entities caught in their downhill flow so long as they export a surfeit of disorder to their environment;
• the laws that enable molecular interactions;
• the laws that enable selection and adaptation;

• those physicochemical laws and inherited information enable operation of a self-organizing system capable of working autonomously in its own behalf for survival and reproduction of its system’s livelihood;

• though autonomous and working in their own behalf, living things cannot escape from changing external conditions threatening their perpetuation; they must exhibit robustness in their organized network dynamics and they must have built-in adaptable mechanisms that maintain their stability;

• they must also be subject to the law of natural selection, which operates to guide ‘living’ toward perpetuation of ‘living’ both in the near future (individual lifespan) and in the distant future, a continuation of a 3.5 billion year tradition of such continuous ‘living’;

• by being subject to natural selection and other dimensions of evolution, living systems generate increasing varieties of living systems, occupy an extreme spectrum of environments, create their own environments (also known as ‘niche construction’), including the Earth’s biosphere, and permit emergence of degrees of complexity capable of sufficient information processing to allow them to ‘experience’ themselves as living systems.

With those mutually resonating principles, we can unpack definitions of ‘life’ typically stated in terms of entities capable of metabolism, reproduction and evolution.

References

Published Collections of Definitions of 'Life' or 'Living Systems'

• Popa R. (2004) Chronology of Definitions and Interpretations of Life. In: Popa R, ed. Between Necessity and Probability: Searching for the Definition and Origin of Life. Berlin: Springer-Verlag 2004: pp. 197-205 Abstract & Link to Full-Text

• Quotes and source-citations from 1885 to 2002 CE

• Barbieri M. (2003) Appendix: Definitions of Life. In: The Organic Codes: An Introduction to Semantic Biology. Cambridge, UK: Cambridge University Press ISBN 0521824141

• Quotes from 1802 to 2002

Further Reading Not Cited in Text

Books and Book Chapters

• Schrodinger E. (1944-2000) What is Life? Cambridge University Press (Canto). ISBN 0-521-42708-8 Text of Chapter 6: Order, Disorder and Entropy

• Prediction of hereditary molecule like a coded periodic crystal. Watson claims inspiration. Stresses open thermodynamic systems key to life.

• Kaneko K. (2006) Life: An Introduction to Complex Systems Biology. Springer, Berlin. ISBN 3-540-32666-9
• Dill KA, Bromberg S, Stigter D. (2003) Molecular Driving Forces: Statistical Thermodynamics in Chemistry and Biology. Garland Science, New York. ISBN 0-8153-2051-5
• Strogatz SH (2003) Sync: The Emerging Science of Spontaneous Order. Theia, New York. ISBN 0-7868-6844-9
• Buchanan M (2002) Nexus: Small Worlds and the Groundbreaking Science of Networks. W.W. Norton, New York. ISBN 0-393-04153-0
• Hoagland M, Dodson B, Hauck J. (2001) Exploring the Way Life Works: The Science of Biology. Jones and Bartlett Publishers, Inc., Mississauga, Ontario. ISBN 0-7637-1688-X

• Wonderful especially for young people. An illustrated text.

• Solé R, Goodwin B. (2000) Signs of Life: How Complexity Pervades Biology. Basic Books, Perseus Books Group, New York. ISBN 0-465-01928-5
• Loewenstein WR. (2000) The Touchstone of life: Molecular Information, Cell Communication, and the Foundations of Life. Oxford University Press, Oxford. ISBN 0-19-514057-5 [Book Review and Reprint of Chapter One ]
• Hoagland M, Dodson B. (1998) The Way Life Works: The Science Lovers Illustrated Guide to How Life Grows, Develops, Reproduces, and Gets Along. Three Rivers Press, New York. ISBN 0-8129-2888-1

• Wonderful especially for young people. An illustrated text.

• Mayr E. (1997) This is Biology: The Science of the Living World. Belknap Press of Harvard University Press, Cambridge, Mass. ISBN 067488468X
• Margulis L, Sagan D. (1995) What is Life? Simon & Schuster. ISBN 0-684-81087-5

Articles

• Hazen R. (2006) The Big Questions: What is Life? New Scientist Issue 2578, 17 November 2006, page 46-51 Full-Text
• Pace NR. (2001) Special Feature: The universal nature of biochemistry. PNAS 98:805-8 Link to Full-Text

Interviews and Commentaries

• Kauffman S. The Adjacent Possible: A Talk with Stuart Kauffman. Interview

See also in Citizendium

• Origin of life
• Evolution of cells
• Systems biology
• Biology

External links not cited above

• "In the Beginning..." (The Economist)

• From the preface: "How life on Earth got going is still mysterious, but not for want of ideas."

• Stanford Encyclopedia of Philosophy entry

• Excerpt from Conclusion: "“Living organisms are autopoietic systems: self-constructing, self-maintaining, energy-transducing autocatalytic entities” in which information needed to construct the next generation of organisms is stabilized in nucleic acids that replicate within the context of whole cells and work with other developmental resources during the life-cycles of organisms, but they are also “systems capable of evolving by variation and natural selection: self-reproducing entities, whose forms and functions are adapted to their environment and reflect the composition and history of an ecosystem” (Harold 2001, 232)."

• Life under extreme conditions.

Appendix A

Specific Characteristics Shared by All Living Things and Not Explicitly Stated Above

Living things share some very specific features not always explicitly stated above. For example,

• all living things descended from a common ancestor;
• only pre-existing cells can "manufacture" new cells;
• only pre-existing multicellular organisms can 'manufacture" new muticellular organisms;
• a membrane encloses every cell, protecting each from dissolution into its external environment;

• the cell membrane contains molecular systems that enables the cell to import usable matter and energy and to export unusable matter and energy, and others that enable it to send and receive signals to and from other cells;

• most cells have an inherited 'blueprint', or 'recipe', for constructing their components, which self-organize to carry out their naturally-selected functions; some become specialized and lose the blueprint (e.g., red blood cells)
• all cells and multicellular systems eventually die.

Appendix B

Selected Definitions of Life Offered by 19th and 20th Century Thinkers

Marcello Bárbieri, Professor of Morphology and Embryology at the University of Ferrara, Italy, collected an extensive list of definitions of “Life” from scientists and philosophers of the 19th and 20th centuries. Those selected below resonate with the systems and thermodynamic perspectives of living systems:

• "The broadest and most complete definition of life will be "the continuous adjustment of internal to external relations". — Hebert Spencer (1884)

• "It is the particular manner of composition of the materials and processes, their spatial and temporal organisation which constitute what we call life." — A. Putter (1923)

• "A living organism is a system organised in a hierarchic order of many different parts, in which a great number of processes are so disposed that by means of their mutual relations, within wide limits with constant change of the materials and energies constituting the system, and also in spite of disturbances conditioned by external influences, the system ts generated or remains in the state characteristic of it, or these processes lead to the production of similar systems." — Ludwig von Bertalanffy (1933)

• "Life seems to be an orderly and lawful behaviour of matter, not based exclusively on its tendency to go from order to disorder, but based partly on existing order that is kept up." — Erwin Schrodinger (1944)

• "Life is made of three basic elements: matter, energy and information. Any element in life that is not matter and energy can be reduced to information." — P.Fong (1973)

• "A living system is an open system that is self-replicating, self-regulating, and feeds on energy from the environment." — R. Sattler (1986)

Appendix C

Textbook mentionables

From the several different perspectives on what constitutes a living system, discussed in this article, one can derive the list of features that biology textbooks often ascribe to living systems:

1. Organization: A temporary organization of interrelated, coordinated, dynamically interacting hierarchy of molecular components within cells, of cellular components within organs and organisms, of organisms within species, and of species within ecosystems—each importing energy and matter, and using it to build, grow and sustain its structural organization for performing the functional activities needed to maintain that organization for reproducing itself.
2. Metabolism: Conversion of imported energy into any or all of the various forms of energy (e.g., chemical, electrical, mechanical, thermal), needed to utilize imported matter for maintaining functional organization.
3. Growth: At certain stages of its life-cycle, cells, organs, and organisms maintain a higher rate of synthesis (anabolism) than breakdown (catabolism) of structure and increase in organizational complexity. Growth occurs largely according to a "plan" for survival and reproduction. Species tend to grow in numbers of individuals as resources and other factors permit.
4. Reproduction: The ability to reproduce itself, for example, the division of one cell to form two new cells. Usually the term is applied to the production of a new individual (either asexual reproduction, from a single parent organism, or sexual reproduction from at least two differing parent organisms), although strictly speaking it also describes the production of new cells in the process of growth.
5. Gain of New Inheritable Traits.: Inheritable diversity, whether adaptive, neutral or disadvantageous, is a common feature of living things, and the starting point for natural selection. (See also:)
6. Adaptation: At the species level, the ability to gain traits through evolutionary processes that improve the members of the species chance for reproductive success; at the individual organism level, the ability to change (e.g., through learning) in ways that improve the individual's chances for reproductive success.
7. Response to stimuli: A response can take many forms, from the contraction of a unicellular organism when touched, to complex reactions involving all the senses of higher animals. A response is often expressed by motion, for example, the leaves of a plant turning toward the sun, an animal chasing its prey, or neuronal action potentials traveling down nerve fibres during thought.
8. Homeostasis: Regulation of the internal environment to maintain a near-constant state in response to perturbations; for example, sweating to cool off.

Exceptions

Not all entities that otherwise qualify as living ordinarily reproduce themselves, though they exist as reproduced living things. Biologists call such living things 'sterile'. Examples include programmed sterility (e.g., worker ants, mules); acquired sterility (due to acquired injury (disease) to the reproductive process; access sterility (lack of reproductive fitness); voluntary sterility (e.g., human couples). Obviously living things with the capacity to reproduce may die before reaching the reproductive stage in their life-cycle. Conversely, non-reproducing individuals may still effect reproduction of copies of their genes by facilitating the reproduction of kin, who share many genes (see kin selection).

Viruses would not qualify strictly as living things, but manage to 'reproduce' in living systems.

One might ask whether a spermatozoon qualifies as a living entity. From the thermodynamic perspective discussed in this article, one might answer affirmatively, as it keeps itself ‘living’ by doing cellular work. It has a compartmentalized internal organization functioning to keep it far-from-equilibrium. In that respect it resembles a motile bacterium. A spermatozoon reproduces, but in a different way than a motile bacterium: it does it through its parent’s progeny, which the spermatozoon plays an essential role in generating. It doesn’t have to hijack a cell’s machinery to reproduce; it cooperates with another cell (an ovum) to generate cells with machinery to reproduce it. Moreover, in reproducing that way, it subjects itself to meiotic crossover variation, just as its parent’s progeny does, contributing to the variation needed by natural selection to perpetuate the process of living on an earth with ever-changing environments.