The Principles of Life

superior insights into the nature of life

Tibor Ganti (1933 – 2009)   Obituary by Eörs Szathmáry

Tibor Gánti, The Principle of Life, Omikk, Budapest 1987

Criteria of life

1. living
2. potentially living but not dead. For example: resting seeds, dried-out or frozen micro-organisms (66)
3. dead (irreversible change from a living to a non-living state)
4. non-living (physical and chemical systems)

1. Real (absolute) life criteria
   1. A living system must inherently be an individual unit
      A system is a unit when it cannot be subdivided without losing its properties. The system has properties that its parts do not have. A living system, for example a cell is a unit, because it cannot be subdivided without loosing living properties. (GK: equals boundary?)
   2. A living system has to perform metabolism
      Metabolism is the entrance of material and energy into the system which transforms them by chemical processes into its own internal constituents (34), (35). Waste products are also produced and eventually leave the system (42),(59). It follows directly from this criterion that viruses are not living because viruses have no metabolism of their own (19), (32), (37), (38), (47), (49), (53) although they can evolve (see figure below).
      • GK: Possible exceptions: (16). Bacteria can be in a temporary dormant state called microbial cyst. An endospore is a stripped-down, dormant, tough, and non-reproductive structure produced by some bacteria; endospores can survive without nutrients (65). Dry Baker's yeast maybe an example of an organism without metabolism. Cryptobiosis is is a metabolic state of life entered by an organism in response to adverse environmental conditions such as desiccation, freezing, and oxygen deficiency (66). It does not contradict the definition of life, because every entity in cryptobiosis was a living entity before the cryptobiotic state. Seeds do not have metabolism, but are 'dormant life' (31), just like spore-like persister cells (33) and the frozen woodfrog (55). Animals in hibernation hardly have metabolism (62). Similarily, many animals have diapause (63) or torpor. Why must a living system have metabolism? (48)
   3. A living system must be inherently stable
      The system remains itself despite changes in the external environment. The dormant seed or frozen tissue culture or dried-out protozoan are stable, are not dead, but are not functioning. They are not reacting to any internal or external stimulus. Inherently stable includes homeostasis and excitability (36).
   4. A living system must have a subsystem carrying information which is useful for the whole system
      Every living system carries within it the information necessary for its origin, development and function. Books carry information, but not about the construction of the book itself (3). The presence of information-carrying subsystems is characteristic of every living system without exception, and is an indispensable criterion for the development of the living world. The information coded in a system becomes real information only if there exists another subsystem capable of reading and using this coded information.
      [GK: I prefer the words 'information necessary for its origin, development and function' (which is a perfect description) above: 'useful for the whole system' ('useful' is too weak). General remarks: (4)]
      
   5. Processes in living systems must be regulated and controlled
      Processes occurring in the system must be regulated to guarantee its continuous existence. In living systems this is by chemical means. Irreversible processes such as growth, multiplication, differentiation, development and evolution are not included in regulation. Therefore a system (a cell) that does not differentiate or multiply is still alive.
      
2. Potential life criteria
   1. A living system must be capable of growth and reproduction
      Sterile animals and plants cannot reproduce, but are living. Old animals do not reproduce, but are still living. Reproduction is neither necessary, nor sufficient for the individual living state. However, reproduction is a necessary condition for the survival of a species and for evolution.
      
      • GK: for a multicellular organism growth means multiplication of its cells. Because growth and reproduction need not be present in a living system, this criterion is not an absolute criterion (1),(5). Most of our brain cells do not divide, but they are not dead. Some cells in a multicellualr organism are in an inactive state, termed senescence, in which they are alive but have permanently stopped dividing. Therefore, the distinction between absolute and potential life criteria is important (20)].
   2. A living system must have the capacity for hereditary change and, furthermore, for evolution, i.e. the property of producing increasingly complex and differentiated forms over a very long series of successive generations
      The criterion for reproduction includes heredity, so heredity is not a separate criterion. However, the capacity for mutation is a separate criterion. Heredity must not be perfect, otherwise evolution could not occur. The capacity for hereditary change is a necessary but probably insufficient condition for evolution.
      • Szathmáry: evolution is not a property of an individual but of a population.
        
      • GK: It is conceivable that heredity produces only identical copies of individuals. Those individuals would still be alive and reproducing. In principle, DNA-copying could be 100% perfect and mutation need not be present (1). On the other hand if DNA-copying of the first cells or animals was 100% perfect, we would not be here (51).
        
      • Griesemer: hereditary differences must have a different survival value to cause evolution.
        
   3. Living systems must be mortal
      Non-living systems cannot die, so death is characteristic of life. Without death organisms would be immortal. Cell division produces two new individuals, the original cell ceases to exist, but does not die.
      
      • GK: animal germline cells, embryonic stem cells, tumor cells and immortalised cell lines are potentially immortal, while body cells are mortal (12). Bacteria are potentially immortal. Therefore, being mortal is not an absolute life criterion (2). Note the conflict with A-3.

The chemoton theory

Relevance of Chemoton model and criteria of life

• Astrobiology / Bioastronomy / Exobiology
  To hunt for signs of life on Mars, the NASA uses the detection of proteins, carbohydrates, membrane lipids and nucleic acids (24). Gánti's chemoton consists of a chemical motor (but not necessarily proteins and carbohydrates), a chemical boundary system (but not necessarily lipids) and a chemical information system (but not necessarily Deoxyribo Nucleic Acid; not necessarily the 4 bases A,T,C,G). This is because Gánti's chemoton is a general, universal definition of life. It is not restricted to life on earth. There could be life with a chemical motor not based on proteins and carbohydrates, with a membrane not based on lipids and with an information system not based on DNA. As long as we do not know what chemicals that could be, we can only look for chemicals that are characteristic for life on earth. However, a way to go is to detect complex molecules, biopolymers that are unlikely synthesized abiotically (52). The situation is different from geologists detecting fossil traces of life in the oldest rocks on earth, because earth-geologists already know that DNA-lipid-protein based life exists on earth. A very interesting contribution to the definition and origin of life is given by astrobiologist Radu Popa. See also: astrobiology.nl and astrobiology.com.
  
• Origin of life research
  If one wants to solve the origin of life, it is extremely helpful to have a good idea about what minimal life is. Gánti shows the way. Some current approaches to the origin of life problem are doomed to fail, because they ignore Gánti's insights. In the origin of life research community usually two schools are distinguished: 'metabolism-first' and 'replication-first'. But life is a cellular phenomenon. The boundary subsystem is missing. However, Koonin proposes geologically formed, inorganic, abiogenic three-dimensional compartments that fulfilled the imperative compartmentalizing function of lipid bilayers and cell walls before the latter arose (50). Nick Lane proposes the origin of life in alkaline hydrothermal vents which are riddled with interconnected pores that have a similar topology to cells (pores are the boundaries).
  
• Artificial Life
  • Digital Artificial Life
    The field of 'Artificial Life' is devoted to investigate whether it is possible to abstract the logical form of an organism from its biochemical wetware (14). Because it abstracts from wetware, I doubt if it can contribute to biology. Life is a chemical phenomenon. Artificial Life mainly focuses on heredity, mutation and differential reproduction, in other words: evolution. A more appropriate name of the field would be 'Artificial evolution', because the field has everything to do with evolution but nothing with life. Something that evolves is not necessarily alive (virus!). Indeed, the field has also been called 'digital evolution' (18). The lack of interest in the question whether digital creatures are alive, further increases my doubt that digital evolution has relevance for biology. Please note the similarity between digital creatures, computer viruses and biological viruses: all evolve but are not alive (67).
    
  • Chemical Artificial Life
    Everybody in 1971, when the first edition of Gánti's book was published, assumed that the creation of life in the lab must incorporate the genetic code and enzymes (13). Gánti showed that this assumption is unwarranted, and then solved the problem that nobody was able to solve. He was a quarter of a century ahead of his time. Today it is no longer a theoretical possibility to construct artificial life. Researchers have started programs to assemble artificial cells from scratch (17, 20). In 2002 Eckard Wimmer synthesized the tiny poliovirus from scratch. In 2008 the genome of the pathogenic bacterium Mycoplasma genitalium (582,970 bases) has been stitched together from scratch (30). See also: Ed Regis (2008) What Is Life? Investigating the Nature of Life in the Age of Synthetic Biology. In 2012 researchers created an autonomous self-regulating, self-powered, homeostatic 'cell' with a bilayer boundary, which seems to possess 4 of the 5 absolute life criteria (excluding a genetic information subsystem) (36).
    
  • Mechanical Artificial Life
    A key feature of biological replication is a template molecule's ability to make copies of itself (as in the case of DNA) by selecting the appropriate building blocks (nucleotides) from parts that are randomly and continuously distributed in its environment; the system also has a built-in ability to correct errors made during copying. Error-correcting replication has been implemented in an artificial system of programmable electromechanical components (25). These systems are not alive according to Gánti's definition, but are units of evolution if error-correcting is not perfect.
    
• Evolutionary biology
  Should evolution (the capacity to evolve) be included in the definition of life? No, says Gánti. One of the advantages of Gánti's distinction between Real and Potential life criteria is that it solves the contradictory properties of viruses, namely (1) viruses are not living (because they do not have metabolism, although viruses have a boundary and a hereditary system), (2) viruses evolve (because their genetic material changes and adapts) (see figure below) (19). Everything that has the capacity to evolve is not necessarily alive (10). The definition of life of John Maynard Smith (9) results in the inclusion of viruses and this is confusing. Many scientists are misled by the contradictory properties of viruses and this prevents a good working definition of life (21). That's why Gánti's definition of life is so important.
  
  

  Overlapping but non-identical sets of units of evolution and units of life . (figure from The Principles of Life, p. 159). Prions and Alife (Artificial Life) could be added to viruses and memes: evolving but not alive (27). Cancer cells could be said to evolve so could be added to the overlap area (GK).

  Genomes sizes of viruses, Bacteria, Archaea and Eukaryota © Science 19 Jul 2013 (37). Note: the genomes of viruses overlap with the other three domains of life.

  
  Pandoravirus has a genome size in the range of free-living bacteria, so the virus is potentially (but not in fact!) a free-living organism. Furthermore, until now it has not been appreciated that viruses have phases. "The confusion between the virus and the virion was first criticized by Claudiu Bandea who considered that the intracellular phase of the virus life cycle is the ontogenetically mature phase of viruses (Bandea 1983). As Bandea wrote in a landmark paper "in this phase the virus shows the major physiological properties of other organisms: metabolism, growth, and reproduction. Therefore, life is an effective presence" (47). This is a major paradigm change of our view of what viruses are. Gánti's definition was based upon the old view of viruses as inert particles. His definition of life can be left largely unchanged, but the virus definition has changed to such a degree that viruses can be considered living. More about this later. See also: Patrick Forterre (2010) below.
  
• Philosophy of biology
  Philosophy is interested in definitions and philosophy of biology is interested in the definition of life. However, philosophical texts are often disappointing in this respect (8) and Gánti has far more interesting things to say about the definition of life. Furthermore, he defined life. Gánti's criteria for life made clear a gap in the Philosophy of biology. No philosopher of biology can ignore him. Here is an urgent task for philosophers of biology and textbook authors. I fully agree with the idea expressed in the title of M. Rizzotti (1996) "Defining Life" is the central problem in theoretical biology (see: Further Reading).
  
• Intelligent Design
  William Paley compared watches and organisms and inferred an organism-designer from the inevitable watch-designer. Paley did not know that living organisms have an internal instruction set to create themselves and that this instruction set changes and consequently new instructions, new individuals and new species emerge. Life creates itself.
  - Intelligent Design and the nature of life: We have seen that life needs, by definition, external energy and food to stay alive. Humans need to consume plants and other animals to stay alive. Why? If the universe is fine-tuned for life, then why is life designed in opposition to the second law of thermodynamics? Why is life opposed (not contradicting!) to the most fundamental law of physics? Why are the laws of physics designed in that way, if (human) life is the purpose of the universe? If humans are the product of intelligent design, then why do humans need to kill to stay alive?
  

Comparison with other definitions of life

• Marilyn J. Roossinck (2023) Viruses, Princeton Univ. Press.
  From the Introduction: Finding a definition that fits all the different types of viruses is difficult. Defining a virus as "a living thing" is controversial. The definition must distinguish viruses from bacteria. The definition of Marilyn Roossinck: "viruses have genomes of RNA or DNA, they require a host for all their functions, they carry the genetic material for many sophisticated functions, and they cannot generate their own energy." (...) "In short, there is no simple answer to the question "Are viruses alive?". There have been many arguments on both sides, but rarely by virologists. In general, virologists find their favorite entities fascinating, and whether they are alive or not has little relevance because they certainly impact the lives of everything on Earth."
  • GK: Remarkable and provocative but also a disappointing statement! Indeed, defining viruses is possible without defining life. So, her position is a non-contradictory logical position. However, it would be helpful to define both viruses and life in order to highlight the differences and similarities between viruses and living things. Also, her definition of viruses is too vague. For example, how can it be that: "they require a host for all their functions" but at the same time "they carry the genetic material for many sophisticated functions". What are those functions? Do viruses have more functions than replication? Many sophisticated functions? So, not all functions? How many essential functions are not coded for by their own genomes? Maybe this is better: "they require a host for executing all their functions, but they carry their own genetic instructions for (many of) those functions". In the chapter 'The diversity of life' there is an evolutionary tree of life (page 31), but viruses are nowhere to be found (69). Maybe life can be defined as all entities that function as hosts for viruses!
• Wallace Arthur (2023) Understanding Life in the Universe: an entity is alive if (1) it has intrinsic metabolism; (2) it belongs to, or is descended from, a group (species) that reproduces sexually, asexually, or through a mixture of the two; and (3) there is inheritance of organismic features from one generation to the next. Because viruses have no metabolism, viruses inhabit a grey area between life and non-life.
  • GK: this is a thoughtful definition. The 'cell' is absent from this definition. His reason: acellular slime moulds. They consit most of their lifespan of a large amorphous structure called a syncytium or 'plasmodium'. These are the only exception to the rule that life is cellular. If we allow 'cells at any stage of the life cycle' in the definition, then cellularity can be included in the definition of life. Criticism: the large amorphous structure may not be a cell, but it must have some kind of boundary. Another feature that is absent is the fact that metabolism is controlled by the genetic material, and that metabolism produces the building blocks for the genetic material and the boundary. In other words: the genetic material has double function: the carrier of heredity and the controller of metabolism. The Gánti definition emphasizes the integration of the 3 components of life. A practical problem: when searching for alien life, the properties 'Inheritance' and 'Reproduction' are not easy to test when a potential alien lifeform is encountered. It necessitates lab experiments to establish real inheritance.
• Carl Zimmer (2021) 'Life's Edge: The Search for What It Means to Be Alive.
  After quoting and discussing several definitions of life, Zimmer ends with a disappointing definition: "Life is what the scientific establishment (probably after some healthy disagreement) will accept as life." (to be continued)
  
• Stuart Bartlett, Michael L Wong (2020) Defining Lyfe in the Universe: From Three Privileged Functions to Four Pillars, Life, 2020. Open Access. [ 21 Oct 2024 ]
  
  • GK: I did not yet finish reading the publication, but I note that Fig.1. ('Three Privileged Functions') are similar to the three components of life in Gánti's definition of life:
    1. Replication: Gánti's Chemical information system
    2. Metabolism: Gánti's Chemical motor system
    3. Compartment: Gánti's Chemical boundary system
    Gánti (1975) is mentioned. Interestingly, the authors note that each of the 3 is proposed by some scientists as the first step in the origin of life. That poses a problem, since they depend on each other. So, when this problem is solved, the origin of life is solved.
• Edward Trifonov (wikipedia page): "A part of Trifonov's work on the molecular evolution is his aim to find a concise definition of life. He collected 123 definitions by other authors Vocabulary of Definitions of Life Suggests a Definition. Instead of dealing with logical or philosophical arguments, he analyzed the vocabulary of the present definitions. By an approach close to the Principal component analysis, he derived a consensus definition: "Life is self-reproduction with variations". This work gained multiple critical comments."
  • GK: Almost identical with Darwin's 'Descent with modification'. Further: it spans different generations of organisms, it is above the level of an individual living organism. So, it has to show reproduction. Furthermore, it seems to ignore asexual reproduction (cloning).
• Eugene Koonin, Yuri Wolf (2012) 'Evolution of microbes and viruses: a paradigm shift in evolutionary biology?' and Koonin (2006) The Two Empires and Three Domains of Life in the Postgenomic Age. Here Koonin sidesteps the question whether viruses are alive, and distinguishes viruses and cellular life on the basis of the presence of certain genetic characteristics:
  • "Viruses typically lack many of the genes that are universal among the three domains of cellular life – in particular, genes for translation system components. However, a small core of viral "hallmark genes" have been discovered that are missing in cellular life-forms. These genes encode proteins essential for virus reproduction (e.g., polymerases, helicases, and core virus particle components). These hallmark genes are shared by an extremely diverse group of viruses with different replication strategies, although none of the genes is strictly universal among viruses. The discovery of the hallmark genes reveals the evolutionary unity of the viral empire (Koonin et al. 2006)."
  • "While cellular life forms all use a uniform replication-expression strategy based on double-stranded (ds)DNA replication, transcription of genes into mRNA or non-coding RNA, and translation of mRNA into protein, viral genome can be represented by all known forms of nucleic acids, and alternative replication processes such as RNA replication and reverse transcription are widely used." (Koonin, 2012)
• Michael Marshall (2020) Nature 9 Dec 2020: "Although there is no standardized definition of life, most researchers agree that it needs several components.
  [1] One is information-carrying molecules – DNA, RNA or something else. There must have been a way to copy these molecular instructions, although the process would have been imperfect to allow for mistakes, the seeds of evolutionary change.
  [2] Furthermore, the first organisms must have had a way to feed and maintain themselves, perhaps using protein-based enzymes.
  [3] Finally, something held these disparate parts together, keeping them separate from their environment."
  • GK: I added numbers. These three principles are similar to Gánti's principles of life. So, it seems that his principles are pretty much the consensus view in science today. Marshall did not refer to Gánti.
  
  
• Paul Nurse (2020) What is life? (64). An extended discussion can be found at korthof.blogspot.com. Paul Nurse defines life with three principles (with my comments):
  1. The ability to evolve through natural selection. To evolve, living organisms must reproduce, they must have a hereditary system, and that hereditary system must exhibit variability. Any entity that has these features can and will evolve.
     • Evolvability belongs according to Gánti to the 'Potential life criteria'. Szathmáry: evolution is not a property of an individual but of a population. 'variability' is a property of a population not of an individual.
  2. life forms are bounded, physical entities.
     • This equals Gánti's Chemical boundary system. It is not clearly stated that the metabolism and information subsystem do create the boundary.
  3. living entities are chemical, physical and informational machines. They construct their own metabolism and use it to maintain themselves, grow and reproduce. These living machines are co-ordinated and regulated by managing information, with the effect that living entities operate as purposeful wholes.
     • GK: His third principle is almost a complete definition of life because two of the three subsystems are included: a Chemical information system and a Chemical motor system.
       According to Gánti growth and reproduction are Potential life criteria: adults don't grow, a non-dividing cell –for example a neuron– is not dead.
       "co-ordinated and regulated" and "maintain themselves" equals Gánti's third Absolute criterion: "A living system must be inherently stable".
       Finally, Nurse's first principle suggests that the only function of the hereditary subsystem is evolvability, and it is not clear that the informational subsystem "is useful for the whole" (Gánti's 4th absolute life criterion) and controls metabolism.
  
  
• Addy Pross (2012,2014) What is Life? (my review).
  Addy Pross did not include membranes in his definition and theory of life: "Yes, cells are central entities in life without doubt, but still just one further link in the complexification process, unable in themselves to offer insight into the central questions in biology: what is life, how did it emerge, and how (in principle) could one make it? Life is the process by which those cells emerged.". This looks a coherent view. I am not sure whether he paid enough attention to the question whether a membrane is necessary in an early phase of the origin of life. However, maybe a disadvantage of Gánti's 3-part model is that it does not give clues how life originated? However, the origin of life and the definition of life are two different questons.
• Patrick Forterre (2010) Defining Life: The Virus Viewpoint, Orig Life Evol Biosph. Apr 2010; 40(2): 151–160. See: § What is Life?
  At the end of the article Forterre arrives at a final definition : "A living organism can thus be defined as: "a collection of integrated organs (molecular machines/structures) producing individuals evolving through natural selection"."
  GK:
  
  • according to Forterre's definition viruses are alive! This contradicts Ganti's definition of life because viruses have no metabolism of their own. Amazingly, the presence of metabolism is not included in his definition of life, despite the fact that the basis of his claim is that viruses are alive when replicating in the host cell. Replication involves metabolism (see: 6).
  • the property "evolving through natural selection" is not an absolute criterion of life. According to Gánti's Potential life criterion B2 living organisms must have the capacity for hereditary variation and to evolve.
  • there is no requirement in this definition for a boundary system. But even viruses have a boundary (capsid).
  • Forterre subsequently writes: "The precise moment when life originated corresponds to the appearance of the first individuals formed by at least two integrated molecular organs (possibly a primitive metabolic network and a membrane) co-evolving through natural selection." However, "metabolic network and a membrane" are absent from his definition of life!
  • The existence of virus-specific proteins (genes) and a possible major role in the origin of cellular life does not make viruses alive. Viruses are important and interesting even if they are not living entities!
  • Maybe the most important objection: Forterre emphasizes that viruses have two phases: a dormant phase outside the host cell (the virion) and a living phase inside the host cell ('the real viral organism'), "in this phase the virus shows the major physiological properties of other organisms: metabolism, growth, and reproduction.". so, it is clear that Forterre accepts metabolism as part of the living state, but omits it in his definition of life!
  To solve this inconsistency, Forterre should add 'metabolism' to his definition. Gánti's definition is unaffected, but his view of viruses should be updated to the modern point of view. Which requires overthrowing a very long tradition in the usage of the term 'virus'.
  
• Robert Shapiro (2007) 'A simpler origin of life'. Scientific American, June 2007, pp. 24-31.
  Shapiro refers to the definitions of life in the Encyclopeadia Britannica and uses the thermodynamic rather than the genetic definition because the origin of a genetic system is too improbable. The thermodynamic definition is: "a localized region that increases in order (decreases in entropy) through cycles driven by an energy flow" and he gives five common requirements:
  1. a boundary is needed to separate life from nonlife
  2. an energy source is needed to drive the organization process
  3. a coupling mechanism must link the release of energy to the organization process that produces and sustains life
  4. chemical network must be formed to permit adaptation and evolution
  5. the network must grow and reproduce
  I note the lack of a clear distinction between definition of life and origin of life hypotheses. Furthermore, if (4) is required to create a complex cell, in other words: evolution, how could that be done without a genetic system? Usually, one requires the ability to evolve, not evolution itself. A system incapable of evolution, could still be alive. Again, a confusing mixture of definition of life and origin of life. Shapiro adds to requirement 5 that "a system of reproduction must eventually develop" (my emphasis). Question: is the system alive before that event? If so, requirement 5 must be dropped from the definition of life. Apart from these remarks, the article is recommended very much (regrettably, it is not freely available online).
  
• Pier Luigi Luisi (2006) The Emergence of Life. From chemical origins to synthetic biology.
  Chapter 2 is devoted to the definition of life. Preferred definition of life is autopoiesis (chapter 8). Includes a comparison with Gánti's chemoton model (p.177). Info: research issues.
• Kevin W. Plaxco & Michael Gross (2006) Astrobiology: A Brief Introduction.
  This introduction to astrobiology appropriately starts with the question: What is Life? Their working definition of life is: "Life is a self-replicating chemical system capable of evolving such that its offspring might be better suited for survival". Gánti would absolutely agree with including 'chemical system', but self-replication and evolution are potential life criteria (B1 and B2). Interestingly, the authors note that self-replication is not necessary for a specimen to be alive (non-reproducing individuals exist!), so self-replication cannot be a litmus test for life. However, self-replication must be applicable to most individuals of a species. Their justification is that all non-reproducing individuals originated from reproducing individuals. Furthermore, they note that evolution acts on the level of populations. Remarkably, the authors state 'the fragile state of chemical disequilibrium we call life' on page 173, but chemical disequilibrium is not in their definition of life. They sum up 5 requirements for the origin and survival of life: 1) suitable atoms, 2) abundance of suitable atoms, 3) a solvent (water), 4) energy, and 5) time. Remarkably, metabolism is not part of their definition, although metabolism is perfectly and uniquely applicable to a potential living individual. Even the more remarkable, because the Viking spacecraft on Mars used radioactive markers to detect carbon-based metabolism (p.221). Please note, that membranes are absent from their definition. Indeed, they claim that replicating and evolving RNA molecules are 'organisms' (p.122). On the other hand, they claim that membranes are 'the key step in creating cellular life' (p.139). Yet, they are aware that even 'RNA-organisms' need to be enclosed by something. Here we see that Gánti's boundary should be included in the definition of life too. Conclusion: their initial definition is incomplete. However, a satisfactory definition can be reconstructed from their book. They do not mention Gánti. Knowing Gánti's definition would have been useful for constructing a working definition of life.
• Schulze-Makuch & Irwin (2006) Life in the Universe. Expectations and Constraints, Springer, paperback, 172 pp. No index.
  In Chapter 2: Definition of Life: they define three fundamental characteristics of life:
  1. composed of bounded microenvironments in thermodynamic disequilibrium with their external environment
  2. capable of transforming energy and the environment to maintain a low-entropy state
  3. capable of information encoding and transmission
  The three elements are close to Gánti's (who is not mentioned). Remarkable: emphasis on membranes, which is often neglected or completely omitted in other definitions: "A major distinction between living and non-living systems is the presence of biomembranes". The definition differs from Gánti by the presence of the words 'thermodynamic disequilibrium' and 'low-entropy state'. As far as I know Gánti does not use these concepts. I am not sure if they belong in a definition of life. A disadvantage of this definition is that the three elements are not well integrated, they are isolated, they don't seem to contribute to the whole.
  
• Stephen Stearns & Rolf Hoekstra (2005) Evolution, an introduction.
  This evolution textbook contains a short section on the origin of life. The authors recognize the importance of defining life, but only give a rough characterization: "a living thing should have metabolism - a coordinated system of chemical reactions contributing to its maintenance, a system that imports energy to maintain order - and hereditary replication - a system of copying in which the new structure resembles the old." (p.357). What is wrong with this definition? (1) the definition ignores the fact that all life is cellular (Gánti's boundary); (2) non-reproducing individuals (mules, sterile individuals, non-dividing cells) are alive; (3) no distinction between absolute and potential life criteria, which explains error 2. For a textbook aimed at students taking a first course in evolution it is really a missed opportunity to teach deep insights into the nature of life. Please note that according to their definition viruses are not alive because of the lack of metabolism.
• Radu Popa (2004) Between Necessity and Probability: Searching for the Definition and Origin of Life. [ Springer info. Contents of the book]
  Popa discusses Gánti's chemoton model in the appendix: "The chemoton model proposed by Tibor Gánti (1971) is one of the most elaborate models of primitive life". Popa discusses nine other theories of the origin of life in the appendix. Astrobiology adds an extra dimension to the definition of life. First: the definition of life is no longer of secondary importance, but a core question to be solved in order to detect life on other planets. Secondly, the definition must be free of earth-bound specifics according. DNA, proteins, lipids, Carbon and water may all be necessary for life on earth, but may not be necessary for life on other planets. DNA does not mean life, only complex chemistry. Lovelock is absent (detect life via the composition of the atmosphere). See also: (29).
• Christian de Duve (2002) Life Evolving - Molecules, Mind, and Meaning.
  De Duve is the 1974 winner of the Nobel Prize in Physiology/Medicine. This magnificent book written for a wider audience has high educational value. There is no explicit definition of what life is, and no distinction between relative and absolute life criteria, despite the fact that the first two chapters are about the What Is Life? question. Of course all the ingredients of the definition are present. His implicit definition of Life is: "Life Is What Is Common To All Living Beings", which has the advantage that it enables the exclusion of a lot of characteristics not common to all life. For example characteristics which are not common to plants and animals (photosynthesis), single-cellular and multi-cellular organisms (lung, brain), prokaryotes and eukaryotes (nucleus), etc. The disadvantage is that this definition is more a task than a result. He elaborates this in subsequent chapters. The central characteristic of life is the ability to 'follow a blueprint'. Additionally, a self-building property. Life's requirements are: raw materials, energy and catalysis. On the whole this is a descriptive approach and this blocks the development of the concept 'minimal life'. He summarises: life is one, life is chemistry, central role of RNA. At the same time catalysis (enzymes) are central to life. He clearly has the knowledge, but just does not produce a compact and complete definition.
  About the origin of life: ATP preceded RNA; RNA preceded DNA and proteins. Proteins were invented by RNA. No metabolism without enzymes, so metabolism is relatively late in the origin of life. The advantages of Gánti's explicit definition are: clarity, completeness, compactness and sophistication.
• Franklin Harold (2001) The Way of the Cell.
  This book deserves a separate review. Harold asks the same question as Gánti and Schrödinger: What is Life? The goal of his book is to identify the essential features that distinguish living organisms from other things. His definition is a combination of (1) Lynn Margulis' autopoietic system and (2) John Maynard Smith's systems capable of evolving: "Life is the property of autopoietic systems capable of evolving by variation and natural selection." The word 'capable' here is crucial: does 'capable' mean that autopoietic systems incapable of evolution are not alive? That seems wrong, because a living cell that (a) is incapable of multiplication or (b) is incapable of evolution is still separated from all physical and chemical systems in a crucial way. Here comes Gánti's distinction between absolute and potential life criteria to the rescue. 'Multiplication' and 'evolution' are not part of his absolute life criteria. From the point of view of the origin of life and discriminating life from physical and chemical systems, autopoietic systems are sufficient as a definition of life. From the point of view of populating a planet one needs reproduction (cell division) and from the point of view of 'adaptation'and 'diversity' one needs the most inclusive definition of life (Harold's evolving autopoietic systems).
• Stuart Kauffman (2000) Investigations.
  "I may have stumbled on the proper definition of life itself", "What must a physical system be to be an autonomous agent?". There are similarities (autocatalysis, work) between Investigations, and Gánti's The Principles of Life. I prefer the latter because of its clarity. Kauffman has a completely different style of writing, often leaving the reader astounded and confused.
• Iris Fry (2000) The Emergence of Life on Earth: A Historical and Scientific Overview.
  Fry is pessimistic about the possibility of a definition of life. The definition will either be too narrow (exclude dormant seed) or too wide (include automobiles and flames). However, the problem of dormant seed can be solved by recognising different states of life (Gánti: 'potential living but not dead') (*). Automobiles do consume fuel and excrete waste products, but they do not use the energy and molecules to maintain their own structure (self-repair). So automobiles can easily be excluded from the definition. Despite her pessimism, she gives the next page a definition that excludes flames and automobiles: "Every living system is organized in a much more complex way than any ordered physical system. The unique character of this complexity lies in the ability of an organism to maintain and reproduce its organization according to specific internal instructions, or information." Fry does not distinguish between real and potential life criteria (Gánti). She is not clear about whether or not evolution (as the capacity for evolution or being the result of evolution) must be included in the definition of life. Watching a chemist-philosopher wrestling with life criteria, convinces me that Gánti's distinction between actual and potential life criteria is certainly a conceptual breakthrough. (*) In other words: individuals often have lifecycles with different phases. A dormant seed is not an organism but a phases in the lifecycle of an organism.
• Christopher Wills & Jeffrey Bada (2000) The Spark of Life. Darwin and the Primeval Soup.
  The title of this book is somewhat misleading, because the book is about the origin of life and is strong in education, science and the key figures in the history of biology. The authors are aware that a definition of life is mandatory. However, they define 'proto-bionts' instead. "Protobionts are certainly not living cells as we know them and probably had few of the characteristics of living cells today". Protobionts are defined as having (1) replication, (2) survival under savage conditions, (3) draw energy from the environment to make energy-rich compounds for the replication process, (4) death. The problem with this definition is that it looks like a definition of (minimal) life, but it is presented as a definition of 'proto-life'. Interestingly, the authors remark that Oparin, the famous Russian origin-of-life researcher, later in his life recognised the importance of membranes for life. Just as Gánti did.
• Lynn Margulis, Dorion Sagan (2000) What is Life?
  Margulis recognises metabolism as the primary characteristic of life, but later mentions membranes as primary for the origin of life (following Morowitz). Viruses are not living, but can mutate and evolve (in perfect accord with Gánti) (she does not note the paradoxical combination of not-living and evolving). A reason is that 'viruses lack sufficient genes and proteins to maintain themselves' (p.18). But that means that genes are important for autopoiesis (=self-maintenance) and that is nowhere explicitly stated. "Replication is not nearly as fundamental a characteristic of life as is autopoiesis". This is also in complete accord with Gánti. She mentions as an example a sterile mule, who cannot reproduce but is alive (p.18). She overlooks the fact that the mule is the product of reproduction, so it owes its existence to reproduction. Furthermore, all the body cells of the mule originated by (asexual) reproduction. So, reproduction is still important, although in another way. "The first autopoietic system, which may have lacked both DNA and RNA, was almost certainly a cell." (p.86). Prophetic remark, but no further details. All the ingredients of the definition and the origin of life are there, but not as clearly and systematically organised as in Gánti's book. The frequently used word 'autopoiesis' is not explained in this book, but in Slanted Truths, chapter 20, page 268, there is a list of 6 properties of autopoietic systems. 'Heredity' or 'reproduction' are not among those 6 properties. Nucleic acids are mentioned, but not what they are doing in the cell. No distinction between absolute and potential life criteria, which could help to include heredity, mutation and evolution as a optional life criteria. What is Life? is a reprint from the 1995 edition. Therefore, Gánti is not mentioned.
• Freeman Dyson (1999) Origins of Life, second edition.
  Dyson defines life as a dual structure: metabolism (proteins) and replication (DNA). He forgets Gánti's third subsystem: membrane (lipids). He 'agrees' with Gánti about the primacy of metabolism. It is useful to read Dyson together with Gánti. The thing I like in Gánti is his attention to the definition of life, which is absent in Dyson.
• Paul Davies (1999) The Fifth Miracle. The Search for the Origin and Meaning of Life.
  Physicist Paul Davies wrote an excellent book about the origin of life for the general reader (biologist and nonbiologist). He is the first author I encountered who presented explicit life criteria. He lists no less than ten: Autonomy, Reproduction, Metabolism, Nutrition, Complexity, Organization, Growth and development, Information content, Hardware/software entanglement, and Permanence and change. Davies makes no distinction between absolute and potential life criteria. One criterion is clearly missing: Gánti's boundary system (membrane), although he knows that life is cellular (Oparin).
• John Maynard Smith, Eörs Szathmáry (1999) The Origins of Life. From the Birth of Life to the Origin of Language.
  In this superb book, the authors present two definitions of life. The first is: "Entities are alive if they have the 3 properties multiplication, variation and heredity (or are descended from such entities)". This definition misses metabolism, moreover a single cell can not have 'variation'. So, this definition fails. However, the addition "or are descended from such entities" nicely handles the sterile mule. The second definition is in terms of metabolism and misses the hereditary component. They end up with the dual nature of life: metabolism and information (just as Dyson, who is mentioned also). The first chapter closes with a page long description of Gánti's contribution. That is unique, because in 1999 no English translation of Gánti's work was available (Szathmáry is Hungarian). All other books about the origin of life do not mention Gánti.
• Ernst Mayr (1997) This is Biology – The Science of the Living World
  Ernst Mayr started his career as an evolutionary biologist and evolved into a historian and philosopher of biology. In this book, he devoted (only) two pages to the distinguishing characteristics of life, but they are instructive. His purpose is to get a list of phenomena that are specific to living beings. He arrives at 'properties' and 'capacities', which are based on those properties. For example, a property is 'evolved programs', and a capacity is 'capacity for evolution'. The distinction properties/capacities is clearly similar if not identical to Gánti's real/potential life criteria distinction. Interestingly, Mayr describes 'evolved programs' as the product of 3.8 billion years of evolution, which is correct, but obviously does not apply to the first forms of life! Furthermore, including evolution ('evolved programs') both in properties and in capacities seems problematic. Apparently, the definition of life depends on whether one describes current life, current + extinct life, or 'essential life'. Remarkably, Mayr lists metabolism as a capacity and not as a property (because of viruses?). Metabolism in Gánti's system is a real (or absolute) life criterion. There are some inconsistencies and redundancies in Mayr's system, but it is interesting to compare his system with Gánti's system.
• Stuart Kauffman (1995) At Home in the Universe. The Search for the Laws of Self-Organization and Complexity
  (my review). There is a similarity between Kauffman's ideas about the origin of life and those of Gánti. On theoretical grounds, Kauffman believes that autocatalytic sets can originate without a genome ("metabolism-first and genes-later" view of the origin of life). Gánti's believes that highly specific enzymes must be later additions to life-like chemical systems ("metabolism-first and enzymes+genes later"). Kauffman's sets can be enzymatic or non-enzymatic. Kauffman believes that specificity arises statistically as an effect of a great number of proteins with random specificity. It is unclear whether Kauffman's autocatalytic sets can be non-enzymatic. According to Gánti non-enzymatic catalysis is not an option because they are out of control of the proto-cell. They are not copied and multiplied as cells divide (pers.comm.). So the question remains whether auto-catalysis based on enzymes is feasible. Kauffman writes fascinatingly, but he uses the abstract language of a physicist and often of a poet. Gánti has an analytic approach.
• James Lovelock (1995) The Ages of Gaia. A biography of our living earth
  Gaia theory says that the earth is a living superorganism. Lovelock recognises the need for a definition of the concept 'life'. Lovelock observes that the Dictionary of Biology has no entry for 'life'! In general biologists avoided the question, he says. However, I disagree that no one has yet succeeded in defining life. Lovelock did not know Gánti's definition. Lovelock attempts to define life, but misses the dual nature of life (metabolism-heredity). On the other hand he quotes Schrödinger's definition: living systems have boundaries and are open systems at the same time. This is a dual nature from another perspective. In the context of thermodynamics: life is a self-organising system characterised by an actively sustained low entropy. Because Lovelock overlooks the importance of 'minimal life' in defining life, he fails to give a thorough and satisfactory definition. A probable cause is his focus on planetary biology and symbiosis (life exists in communities and collectives). The lack of a good definition of minimal life prevents a good understanding of problems inherent in the origin of life. For example when discussing the origin of life, he states "The first living cells may have used as food the abundant organic chemicals lying around; also the dead bodies of the less successful competitors..." (p.72). However, by definition, the first forms of life could not have used dead bodies.
• Mark A. Ludwig (1993) Computer viruses, Artificial Life and Evolution
  Although physicist and anti-Darwinist Mark Ludwig is sceptical about the possibility to give a list of defining characteristics of life, he presents a list used by artificial life researchers: 1) the ability to reproduce, 2) emergent behavior, 3) metabolism, 4) ability to function under perturbations of the environment and interact with the environment, 5) ability to evolve. This list is a mix of real life criteria (#3,#4) and potential life criteria (#1,#5) according to Gánti's life criteria. That explains his problems. Ludwig states that the approach of refusing to call something alive unless it can evolve is rather blind (I agree). He claims that evolution cannot be used as a dividing line between life and non-life (I agree), but he does so for the wrong reasons (creationist argument: it cannot be observed). The correct reason is that living individuals have the potential to reproduce and evolve (#1,#5), but need not actually do it. That's why reproduction and evolution are potential life criteria. Remarkably, Ludwig claims that computer viruses can be designed to show Darwinian evolution (I agree). Because Ludwig does not make the important step of discriminating between the non-overlapping units of life and units of evolution, he is driven to the conclusion that from a mechanical perspective, it seems safe to say that computer viruses have a fairly strong claim to "life" (I disagree). In the Gánti definition neither biological nor computer viruses are alive. Furthermore, Ludwig does not distinguish between the properties self-reproduction and information system. This prevents him making an information subsystem a primary life criterion. Secondly, it prevents him from moving self-reproduction from primary to secondary criterion of life. (my review of his book).
• Harold Morowitz (1999) 'A Theory of Biochemical Organization, Metabolic Pathways, and Evolution', Complexity pp 39-53. (article free download).
  This looks like a definition of life: "Associated with self-replicating far-from-equilibrium systems is an energy requirement. There is a constant thermal degradation, driven by the second law of thermodynamics, toward equilibrium that must be countered by the expenditure of work. Thus, there is the requirement of a proper energy source and the ability to convert that energy into a form that is useful in maintaining the structure and synthesizing similar structures."
  Gánti does not mention "far-from-equilibrium" although it gives a reason why "A living system has to perform metabolism" (A2). A3: "A living system must be inherently stable" seems to contradict the inherent unstable far-from-equilibrium state of living organisms. However, it can be interpreted as a living system must have continuity. B3: "Living systems must be mortal" seems to capture the far-from-equilibrium status, because when food intake stops, the organism dies and its molecules are in equilibrium.
  
• Harold Morowitz (1992) Beginnings of Cellular Life: Metabolism Recapitulates Biogenesis
  Lynn Margulis (2000) gives a description of Morowitz theory. According to Morowitz, neither DNA nor RNA alone is enough to form life. Membranes arose before proteins and nucleic acids. A membrane represents the transition from nonlife to life. All forms of metabolism and the synthesis of proteins and nucleic acids evolved only after membranes enclosed the precursors of cells. A non-aqueous barrier was necessary to separate the cell from its surroundings. There seems to be a problem with this scenario. If a membrane must be produced before any metabolism is in place, then the suitable lipids must be produced abiotically. Can they be produced without enzymes? Morowitz is an important and original researcher in the origin of life field and although I do not know enough details, his views seem to show great similarity with Gánti.
  
• Hubert Yockey (1992) Information theory and molecular biology
  Obviously, for Yockey, information is a very important defining characteristic of life. Otherwise he would not have written such a book. But how important? "The essential difference between living and non-living matter is that the formation and function of important biological molecules is governed by genetic messages. No trace of a comparable specification by sequences or of a code between sequences exists in non-living matter" (Prologue). This is based on Mayr (1988). I summarised this view as "Information is the essence of life" in a review of his book. Yockey does not discuss the matter further (there is no chapter or paragraph devoted to the question). This is not a complete definition of life. It seems that viruses are living according to this definition.
• Robert Shapiro (1986) Origins. A Skeptic's Guide to the Creation of Life on Earth
  A very useful book, but also lacks an explicit discussion of the definition of life. On page 132 I noticed components of life: 'the membrane, the energy-generating system, the genetic system, the vital catalysts', but I don't know whether Shapiro discussed them earlier in the context of the definition of life. Note that the first 3 are identical to the 3 components of Gánti's chemoton model. The following quote from Shapiro shows an implicit definition of life and one that is clearly opposed to Gánti's definition: "It becomes important, then, to find the simplest possible self-reproducing, or replicating, system, for this would be the first living thing (emphasis added). (this is according to the 'naked gene' theory of the origin of life). Again, I notice a similarity between Gánti and Kauffman: both oppose the 'naked gene theory'.
• John Maynard Smith (1986) The Problems of Biology
  This is one of his first books for the general reader. Concise and well written. A beautiful opening chapter 'the definition of life'. An indispensable topic if one wants to introduce readers to biology. Scientists like Tibor Gánti brought the subject to a superior level of sophistication, but what JMS has to tell us, is still of great value. His definition is "entities with the properties of multiplication, variation, and heredity are alive, and entities lacking one or more of those properties are not". Fire consumes external energy, continuously changes its internal substance (metabolism), can multiplicate itself and it varies, but since it lacks heredity, it is not alive. Therefore it can not evolve by natural selection and cannot acquire organs to keep it going. Adaptation is all about organs that help an organism to survive. Any adequate theory of evolution must explain adaptation. I think a definition of life does not need to explain life. It is necessary and sufficient that it includes all living objects and excludes all non-living objects. Fire has no parts that help it survive, so it can be rejected whether or not is has heredity.
• 
  31 Jul 23
  Eli C. Minkoff (1984) Evolutionary Biology
  Minkoff gives the following definition of life:

  "A thing is living if, at some time during its existence, it exhibits metabolism, irritability, homeostasis, growth, and usually also some form of motion, and if it belongs to a population of similar organisms, of which at least some must be capable of reproduction." (p.3)

  This is very careful definition. It introduces conditional phrases like 'at some time during its existence' to account for dormant phases. The phrase 'at least some must be capable of reproduction' accounts nicely for non-reproducing individuals of the species.
• Francis Crick (1981) Life Itself. Its Origin and Nature
  Chapter four of this book, 'The general nature of life', contains a concise and splendid description of the nature of life with an unsurprising emphasis on replication. The result is that metabolism and membranes become almost accessories. However, Crick has a very good reason why life needs membranes: cells with useful genes are able to prevent that other cells take advantage of their genes. Unlike Gánti, Crick does not distinguish between life as such and life capable of evolution. According to Crick's definition of life, chemical systems without an informational subsystem or with 100% accurate (error-free) replication, would not be living systems.

1. God could have created every individual directly and without the capacity for reproduction. Two effects of reproduction destroy perfect design: recombination and mutation. Recombination creates new combinations and mutation mutates what is perfect and this means less perfect. God could prevent hereditary diseases, congenital defects, spontaneous abortion, ageing, etc by creating each individual directly. Evolution would not be possible, but then, who needs evolution when one is directly created by God? See Swinburne review ('Four ways to create life').
2. God could have created every individual without death and ageing. "Cell aging and death is not an obligatory attribute of life on earth" (W.R. Clark, 1996). But then evolution would not be possible, because death is a necessary condition for evolution on a finite planet. But who needs evolution if one is directly created by God and if one is immortal?
3. Paley's watch has an internal structure, but does not carry internal information about its construction! That's why it cannot reproduce itself. See Swinburne review.
4. If one equals 'life' with 'information', then creating life equals the creation of information. William Dembski, Hubert Yockey and Periannan Senapathy fall in this trap. However, Tibor Gánti shows that information is only one of the 3 subsystems of living systems. Information is meaningless without the other two subsystems. Manfred Eigen (1996) Steps towards Life, also has an information-centred approach to the origin and evolution of life, but mentions the importance of compartments.
5. If reproduction would be included in the absolute definition of life, then homosexual and all other non-reproducing individuals would not be alive. See review of Bagemihl.
6. Szathmáry is co-author with John Maynard Smith of the important The Origins of Life. From the Birth of Life to the Origin of Language (see review).
7. Periannan Senapathy constructed a theory which is based on the idea that single-celled as well as multicellular organisms could originate directly from non-living materials. This is rejected by every biologist.
8. Kim Sterelny and Paul Griffiths (1999) Sex and Death. An Introduction to Philosophy of Biology, with the last chapter (15) "What is Life?". Amazingly (!), they refuse to give a definition of life: "We do not see how a definition of 'life' is likely to help us with odd and hard-to-classify cases: prions, viruses, social insect colonies, or the much less plausible idea that the earth itself is a living system" (p.358) and in stead they try to define 'universal biology'. Gánti is not mentioned (of course), and there is nothing similar to Gánti's life criteria, which is a serious omission for a philosophy of biology textbook.
9. JMS's definition: "Entities are alive if they have the properties of multiplication, variation, and heredity or are descended from such entities" is indeed a mix of 'life' and 'evolution'.
10. Jens Burmeister in Brack (1998) The Molecular Origins of Life confuses 'life' and 'evolving system' and produces an implicit definition of life: "In general, an evolving system is able to metabolize, to self-replicate, and to undergo mutations. Thus self-replication is one of the three criteria that enable us to distinguish non-living from living systems." (p.295). He switches, without noticing, from 'evolving systems' to 'living systems'. An organism without mutations is not alive? That is why we need explicit definitions!
11. There is a snag. The basic cell membrane alone would have been useless. Surrounding a self-replicating molecule with a lipid bilayer would prevent dispersal of most of the products of any reaction; but it would also prevent access to essential raw materials. Real cell membranes contain a host of pumps, channels, gates and pores. Ian Glynn (1999) An Anatomy of Thought, p.78.
12. The famous HeLA-cell line, a human tumor cell line, kept growing indefinitely. William R. Clark (1996) Sex and the Origin of Death, pp 93-97.
13. In 2002, human genome sequencer Craig Venter announced his plan to build an artificial cell with a minimal genome based on modern genes. According to Koonin, the minimal set of genes will number about 600 (Nature 19 Feb 2004). Building artificial life would be a huge success, a milestone in the origin-of-life-research, but how does a minimal set of 600 genes arise? Gánti could bridge the gap between life-with-a-minimal-genome and life-without-a-genome.
14. Christopher Langton in Artificial Life (1989), p.21. There is also a scientific journal Artificial Life (MIT Press). See also: The Digital Life Laboratory for a description of digital life.
15. John Maynard Smith said about Eörs Szathmáry: "he really knows molecular biology and chemistry".
16. A possible exception are the Chlamydiae (Eubacteria) because they have no energy metabolism at all, and depend on their hosts for ATP. So if the production of ATP is an essential property of life, then Chlamydiae are not living! See: Peter Skelton (1993) Evolution. A Biological and Palaeontological approach, page 881. From wikipedia: "bacterial species such as rickettsia and chlamydia are considered living organisms despite not having metabolism".
17. Steen Rasmussen, Liaohai Chen, David Deamer, David C. Krakauer, Norman H. Packard, Peter F. Stadler, and Mark A. Bedau, "Transition fron nonliving to living matter", Science. (see website: protocells).
18. "Whether or not these digitals are truly alive is ultimately of no concern to us as researchers: We use them because we are interested in complicated and vexing questions of evolutionary biology, and digitals offer us the possibility to attack them." quoted from Artificial Life. (MIT PRESS)
19. Nature News item: Giant virus qualifies as 'living organism'. About a giant virus which qualifies as living organism, because it can reproduce independently and make its own proteins. So far this is an exceptional virus. It does not mean that all viruses are alive. Nature online 14 Oct 2004. See also: Didier Raoult et al (2004) The 1.2-megabase Genome Sequence of Mimi virus, Science 19 Nov 2004. The Mimivirus has 911 genes, which is an extremely high number for a virus.
    Further reading: Helen Pearson (2008) 'Virophage' suggests viruses are alive, Nature, 7 Aug 2008. The name of the virus is Acanthamoeba polyphaga mimivirus and it can be infected by a small virus, a 'Virophage'. "It crossed the imaginary boundary between viruses and cellular organisms." (Eugene Koonin). I would like to know whether the virus has a metabolism (produces ATP). Raoult, Koonin and their colleagues report the isolation of a new strain of giant virus from a cooling tower in Paris, which they have named mamavirus because it seemed slightly larger than mimivirus.
20. Philip Ball (2004) "Artificial cells take shape", Nature 6 Dec 2004, writes: "These synthetic cells are not fully alive, because they cannot replicate or evolve." They may not be alive, but for other reasons. Being able to divide is a potential and not an absolute life criterion. Apart from this mistake, the article is useful.
21. Louis P. Villarreal (2004) Are viruses alive?, Scientific American, December 2004, pp 77-81 (not available anymore for free, but see below). The article is useful, but I have a few comments. Villarreal does not mention the important insight of The Principles of Life that viruses have the contradictory properties of not being alive, and the ability to evolve. Furthermore, Gánti's definition of life could clarify his discussion of viruses far more than the confusing quotes accompanying the article. Regrettably, Villarreal fails to point out that the strongest argument for the connection of viruses with 'the web of life' is that viruses have the same genetic code as all forms of life on earth. Interestingly, Villarreal wrote a book about the role of viruses in evolution: Viruses and the Evolution of Life (2004). His definition of life is (reprint Sc. Am. Dec 2008):
    • "A precise scientific definition of life is an elusive thing, but most observers would agree that life includes certain qualities in addition to an ability to replicate. For example, a living entity is in a state bounded by birth and death. Living organisms also are thought to require a degree of biochemical autonomy, carrying on the metabolic activities that produce the molecules and energy needed to sustain the organism. This level of autonomy is essential to most definitions."
22. Eörs Szathmary (2005) In search of the simplest cell, Nature, 433, 469-470, 3 Feb 2005. Szathmary recognises the following approaches to the minimal-cell-problem: top-down, bottom-up, RNA-based, lipid-based, theoretical, experimental. Top-down approaches [stripping] seem to point to a minimum genome size of slightly more than 200 genes.
23. Later I kindly received from professor Gánti what seems to be the first book in the English language: The Principle of Life published in 1987 in Budapest (sixth edition). I guess it was not distributed widely. The first (1971), second (1978), third (1979), and fourth (1983) edition were published in Hungarian (Az Elet Principuma) and the fifth edition (1986) in Polish. The English edition is still worth reading: it was aimed at the wider public.[ 18 Feb 2005 ]
24. David L Chandler (2005) , Robotic rover detects life in the driest desert, New Scientist, 16 March 2005.
25. Saul Griffith, Dan Goldwater, Joseph M. Jacobson (2005) Self-replication from random parts, Nature, 437, 636 (29 September 2005). Editor's Summary.
26. However, if enzymes and genetic code are not necessary, then there is no point at all in having an information system (like DNA). If it is not controlling the synthesis of proteins, then what is it doing? See note 40. I later found out that Kauffman's minimalist forms of life also don't have enzymes and genes: Stuart Kauffman: A World Beyond Physics. Review..
27. Prions could be defined as self-reproducing proteins. Prions could evolve if copy errors occur. Artificial Life is potentially evolving non-biological 'life'.
28. Nick Lane (2005) writes: "the enzyme reaction is catalysed by the mineral [iron, sulphur, manganese, copper, magnesium, and zinc], not the protein, which improves the efficiency rather than the nature of the reaction", Power, Sex, Suicide p.95.
29. Radu Popa (2002) A hierarchical model of the emergence of life as a both probabilistic and deterministic conjecture, poster presented at Second Astrobiology Science Conference, April 7 - 11, 2002. Contains advanced definition of life.
30. Philip Ball (2008) 'Genome stitched together by hand' , Published online 24 January 2008 Nature.
    "The genome of the pathogenic bacterium Mycoplasma genitalium has been stitched together from scratch, creating a full set of instructions to make a living thing in the lab."
31. Ann Pearson (2008) 'Biogeochemistry: Who lives in the sea floor?', News and Views, Nature 454, 952-953 (21 August 2008) Published online 20 August 2008.
    Archaea and Bacteria in the seafloor ('deep biosphere') live at the limits of energetic viability. "Part of the problem lies in the distinction between 'living' cells, total cells (including inert or dead cells), and/or cells that are in between, persisting in an undefined degree of stasis. This leads to ambiguity about what should or should not be counted. (...) The fluorescent stains acridine orange and DAPI detect all cells - alive or dead - that contain any remnant of DNA." A method is to detect ribosomal RNA (rRNA) or intact polar lipids (IPLs) of cell membranes (both are proxies for live cells). (...) Polar lipids are presumed to reflect living biomass, because their labile (often phosphate-containing) head groups are quickly lost after cell death. (...) It is therefore reasonable that in a sub-seafloor world, where it has been estimated that cell turnover times could be centuries or longer, organisms with honed strategies to conserve energy would dominate. (...) For microbes, the boundary between alive and dead is fuzzy, and the extent to which any category of biomolecule can define it remains unclear."
32. "In 2000, the International Committee on Taxonomy of Viruses officially declared that viruses are not alive. The genetic makeup of the Mimivirus has challenged this view. The viral giant is endowed with many genes encoding the enzymes that repair DNA, correct errors occurring during its replication, produce mRNA transcripts from genes, and translate those mRNAs into proteins. These so-called informational genes had so far been considered hallmarks of living things." From: Catherine Mary (2012) 'Giant Viruses Revive Old Questions About Viral Origins', Science 2 Mar 2012. p. 1035.
    "The only characteristic that distinguishes the Mimivirus genome from a cellular genome is the absence of genes encoding ribosomal proteins.": Patrick Forterre (2010) "Giant Viruses: Conflicts in Revisiting the Virus Concept", Intervirology June, 2010.
    See also note 53.
33. Kim Lewis (2012) 'Antibiotics: Recover the lost art of drug discovery', Nature 24 May 2012: When challenged, "bacteria produce a small quantity of dormant, spore-like persister cells. The only function of dormant persisters is survival; once the antibiotic concentration drops, persisters wake up, start propagating and the infection relapses." See also: spore.
34. "By definition, metabolism is a process largely concerned with the generation of energy by catabolism [break down molecules into smaller units] and the anabolic manufacture of cellular and extracellular constituents [from smaller molecules]. Metabolism represents the essence of how organisms interact with their environment and, in doing so, overcome the thermodynamic mandate to 'feed upon negative entropy'", De-Meaning of Metabolism, Mitchell A. Lazar, Morris J. Birnbaum, Science 29 June 2012.
35. quote: "Formation and breakage of chemical bonds underlie all life processes" from: Teruya Nakamura et al, Watching DNA polymerase η make a phosphodiester bond, Nature 487, 196–201 (12 July 2012)
36. Ximin He et al (2012) Synthetic homeostatic materials with chemo-mechano-chemical self-regulation, Nature 487, 214–218 (12 July 2012).
    This is their 'definition' of life: "Living organisms have unique homeostatic abilities, maintaining tight control of their local environment through interconversions of chemical and mechanical energy and self-regulating feedback loops organized hierarchically across many length scales. In contrast, most synthetic materials are incapable of continuous self-monitoring and self-regulating behaviour".
37. (see also: note 19, 32, 38). Elizabeth Pennisi (2013) 'Ever-Bigger Viruses Shake Tree of Life', Science 19 Jul 13. pandoraviruses: "It is clear that the paradigm that viruses have small genomes and are relatively simple in comparison to cellular life has been overturned. ... The genome of one of the viruses is 1.91 million DNA bases long, while the other runs 2.47 million bases." Both pandoraviruses lack genes for energy production and can't actually produce a protein on their own, fulfilling the definition of virus. GK: so it is still true that viruses are not living but do evolve.
38. Nadège Philippe et al (2013) Pandoraviruses: Amoeba Viruses with Genomes Up to 2.5 Mb Reaching That of Parasitic Eukaryotes, Science 19 Jul 2013.
    "The failure to detect components of the basic cellular functions—i.e., protein translation, adenosine 5´-triphosphate generation, and binary fission—confirmed the viral nature of Pandoraviruses. P. salinus possesses none of the ribosome components (RNAs and proteins) and no enzyme from the glycolysis pathway or the Krebs cycle."
39. The importance of a boundary: "Szostak became convinced that RNA couldn't have done it alone. The molecules needed to be isolated and confined. Some sort of cell membrane probably was needed, both to concentrate the ingredients of life and to promote a Darwinian process. "If [chemistry] is compartmentalized, you keep molecules related by descent together," Szostak explains. If an RNA-containing protocell arises and can grow and divide better than its neighbors can, it can pass its advantages to its progeny. The protocells would allow fitter molecules to flourish, in true Darwinian fashion." Robert F. Service (2013) 'The Life Force', Science, 29 Nov 13.
40. If the information carrier is DNA, then it is useless because DNA needs to be translated to proteins (enzymes) to do anything useful. On its own, DNA is dead. However, if the information carrier is RNA then it can function both as a carrier of heritable information and as a catalyst of chemical reactions (Szostak model of the origin of life). Is the enzym-dna-free chemoton model in fact an RNA-world system? In fact, Gánti wrote in 1989: "Experts dealing with the genesis of life and chemical evolution agree that the primordial genetic material was RNA and not DNA" (chapter 2, p. 39). [ 11 Dec 2013 ]
    Taking it one step further, Niles Lehman writes: "The RNA World is a proposed time in the history of the Earth when all the features of life: replication, metabolism, homeostasis, etc., were manifest in RNA molecules" . However, when 'all the features of life' are present then the RNA-world is alive! [ 7 Aug 2014 ]
41. Both RNA and DNA contain information. In the RNA-world, the information in RNA determines directly the RNA 3D-structure. In the DNA-protein world the information in DNA determines indirectly the 3D-structure of proteins. But there is no relation between the two types of information, because bases in RNA determine its 3D-structure in a totally different way than amino acids determine 3D protein structure. There is no gradual evolution from information in the RNA-world to the DNA-world precisely because the two types of information are incompatible. [ 7 Jan 2014 ]
42. I overlooked the fact that Gánti mentioned waste products in his definition of metaoblism in § 3.5.1 (page 76). Waste products are an important aspect of life. For example: oxygen is waste for plants but food for animals, while CO2 is waste for animals, but food for plants. Also, according to Tyson in his TV documentary Cosmos mentions that the production of lignin was a huge problem because at the time no organism could digest lignin. It lasted millions of years before microorganisms could digest lignin. See also: Niche Construction. [ 11 May 2014 ]
43. However, iron and magnesium are the preferred catalysts in primordial organisms, both were abundant and available. Barrow et all (eds) (2008) Fitness of the Cosmos for Life, p.463.
44. However, see Christian de Duve (1995) Vital Dust, 'Catalysis without proteins', p. 26-30. [ 13 Jun 2014 ]
45. No specific molecules such as proteins, nucleic acids, carbohydrates, and lipids are included. This abstractness makes the model not suitable for detecting life on Mars! [ 7 Jul 2014 ]
46. "Shell A [core metabolism] lacks any conventional biological enzymes. Hence, a pre-enzymatic (prebiotic) shell A would have to proceed without the usual catalytic functions as presently constituted. The extent to which this nonenzymatic chemistry is possible in aqueous media is an experimental question and is currently being investigated." Harold Morowitz (1999) 'A Theory of Biochemical Organization, Metabolic Pathways, and Evolution', Complexity pp 39-53. [ 7 Jul 2014 ]
47. "For a growing number of evolutionists and virologists, viruses should definitely be considered as living entities since they exhibit all features typical of terrestrial life: they are made of the same macromolecules as cells from archaea, bacteria or eukarya, and they have co-evolved with members of these three domains according to the scheme of Darwinian evolution." Patrick Forterre (2010) Defining Life: The Virus Viewpoint. However, virusses do not have metabolism, so they cannot harness energy for maintaining their structure and replication. Forterre has an imprecise, ambiguous definition of life. Part of the definition is that virusses enter cells!? If a virus is living, then a mitochondrion is also living? [ 12 Jul 2014 ]
48. Why must a living system have metabolism? Gánti does not mention "far-from-equilibrium" although it gives a reason why "A living system has to perform metabolism" (A2). A3: "A living system must be inherently stable" seems to contradict the inherent unstable far-from-equilibrium state of living organisms. However, it can be interpreted as a living system must have continuity. B3: "Living systems must be mortal" seems to capture the far-from-equilibrium status, because when food intake stops, the organism dies and its molecules are in equilibrium. See: Harold Morowitz (1999) above. [ 20 Jul 2014 ]
49. "Viruses were defined as one of the two principal types of organisms in the biosphere, namely, as capsid-encoding organisms in contrast to ribosome-encoding organisms, i.e., all cellular life forms.". Eugene V. Koonina and Valerian V. Doljab (2014) Virus World as an Evolutionary Network of Viruses and Capsidless Selfish Elements, Microbiol. Mol. Biol. Rev. June 2014 vol. 78 no. 2 278-303. So, here Koonin assumes that viruses are organisms. Also he writes "Genetic parasites, i.e., viruses and virus-like selfish elements", where I would write 'metabolism-parasites', because they carry their own genetic information although not complete (not 'informationally self-sufficient') and not their own metabolism. Metabolism is completely absent in Koonin's review, as if energy is for free.
50. Eugene V. Koonin, William Martin (2005) On the origin of genomes and cells within inorganic compartments, Trends in Genetics, Volume 21, Issue 12, December 2005, Pages 647–654.
51. "All organisms possess a certain degree of evolvability, i.e., the ability to evolve. At the most basic level, evolvability stems from the theoretical impossibility of error-free replication. Genomic variation in evolving organisms is created by a combination of intrinsic replication errors, recombination and mutations induced external agents (mutagens)." "Evidence in support of 'evolvability of evolvability' is mounting". from : Eugene V. Koonin and Yuri I. Wolf (2012) Evolution of microbes and viruses: a paradigm shift in evolutionary biology?.
52. Christopher P. McKay, Victor Parro García (2014) How to Search for Life on Mars , Scientfic American, 2014.
53. David Moreira, Purificación López-García (2009) Ten reasons to exclude viruses from the tree of life, Nature Reviews Microbiology: "Here, we contend that there is strong evidence against the notion that viruses are alive". "Futhermore, that viruses are not alive was officially acknowledged by the International Committee on Taxonomy of Viruses in 2000 and is still held by most virologists." "Here, we examine this evidence and argue, first, that viruses are not true living entities."
54. Mycoplasma are bacteria that lack a cell wall, but they have a cell membrane. The membrane is made of 60% to 70% protein with the remaining 20% to 30% being lipids. (Mycoplasma are the smallest living cells yet discovered.)
55. Woodfrog, Rana sylvatica. See also: How Arctic Frogs Survive Being Frozen Alive, National Geographic, August 21, 2013. The wood frog stop breathing and their hearts stop beating entirely for days to weeks at a time in winter. The frogs' physical processes–from metabolic activity to waste production–grind to a near halt.
56. Tibor Gánti (1975) 'Organization of chemical reactions into dividing and metabolizing units: the chemotons', Biosystems 7 189-195. He already uses: "three subsystems, i.e. into the cytoplasma, the genetic material and the ceell membrane" ... These chemical supersystems are referred to as Chemotons by us (Gánti (1971)". [ 8 Sep 2014 ]
57. "A minimal cell can be thought of as comprising informational, compartment-forming and metabolic subsystems." is the first sentence of the Abstract of the article Common origins of RNA, protein and lipid precursors in a cyanosulfidic protometabolism by John D. Surtherland et al in Nature Chemistry 16 March 2015. Tibor Ganti is mentioned as the inventor of the tripartite definition of life, but the authors note that this begs the question 'did the subsystems emerge together, or one after the other at the origin of life?'. [ 18 Mar 2015 ]. Yes, it begs the question, because Gánti's 3-part system is a definition of minimal life, not a theory about the how the 3 subsystems come together. See also: Researchers may have solved origin-of-life conundrum by Robert F. Service, Science News 16 Mar 2015. The same article appeared as: 'Origin-of-life puzzle cracked' in Science 20 Mar 2015.
58. This is easier said than done. It is difficult to imagine how a non-protein, non-DNA system consisting of the 3 subsystems could evolve into a 3 part system with DNA, genetic code and proteins (enzymes). By the way, a RNA-world could be a viewed as a system consisting of an informational and a metabolic subsystem. [ 20 Mar 15 ]
59. Nick Lane lists the excretion of waste "as one of the six basic properties to make a cell. The excretion of waste is necessary to pay the debt to the second law of thermodynamics and drive chemical reations in the correct direction". "For any reaction to continue in a forward direction, the end product must be removed. If these waste products are not physically removed from the cell, they prevent the forward reaction from continuing." Nick Lane (2015) The Vital Question: Why is Life the Way it is?, chapter 3. [what about recycling waste?] [ 4 May 15 ]
60. This is what I found in Nature Chemisry: "A minimal cell can be thought of as comprising informational, compartment-forming and metabolic subsystems." These are exactly the 3 subsystems of Tibor Gánti and the article also uses the concept 'minimal cell"! A coincident? Article: Common origins of RNA, protein and lipid precursors in a cyanosulfidic protometabolism, 16 March 2015. [ 26 Apr 18 ]
61. Gánti's approach is: something is alive or it is not. There is nothing halfway. This is in contrast to the approach of a fuzzy logic: Gilles Bruylants, Kristin Bartik, Jacques Reisse (2011) Prebiotic chemistry: A fuzzy field, Comptes Rendus Chimie, Volume 14, Issue 4, April 2011. They introduce a scale of 'livingness'. I think it is a valuable addition to the definition of life. [ 22 May 2019 ]
62. Hibernation is a state of inactivity and metabolic depression in endotherms. See Hibernation.
63. Diapause is a state is the delay in development in response to regularly and recurring periods of adverse environmental conditions. It is considered to be a physiological state of dormancy. See wikipedia article Diapause. [ 21 Feb 2020 ]
64. Paul Nurse (2020) What is life? David Fickling Books. Also as ebook. [ 29 Nov 2020 ]
65. Endospore. The endospore consists of the bacterium's DNA, ribosomes. Endospores can survive without nutrients. They are resistant to ultraviolet radiation, desiccation, high temperature, extreme freezing and chemical disinfectants. Reactivation of the endospore occurs when conditions are more favourable. Germination involves the dormant endospore starting metabolic activity and thus breaking hibernation. [ 9 Dec 2020 ].
66. Wikipedia: "Cryptobiosis or anabiosis is a metabolic state of life entered by an organism in response to adverse environmental conditions such as desiccation, freezing, and oxygen deficiency. In the cryptobiotic state, all measurable metabolic processes stop, preventing reproduction, development, and repair. When environmental conditions return to being hospitable, the organism will return to its metabolic state of life as it was prior to the cryptobiosis". An exampe in the plant kingdom is the rose of Jericho or "resurrection plant" (Selaginella lepidophylla). A Resurrection plant is a plant that can survive extreme dehydration, even over months or years. It is potentially living but not dead. So, this causes no problems for the definition of life.
    Cryptobiosis is like a car in a garage or a plane in a hangar or a powered-down computer. [5 Jul 2021]
67. Similarities and Dissimilarities of Computer Viruses and Biological Viruses is a page on this website. [5 Sep 2022]
68. Can there be a chemical information system that is not based on DNA or RNA? This seems to be a problem. On what molecules is such a hereditary system based? How does it work? The editors write on page 144: "Because Gánti has already shown that chemotons multiply, can vary, and have heredity, they satisfy Maynard Smith's criteria for units of evolution." [29 Sep 2022]
69. Hugh M. B. Harris, Colin Hill (2020) A Place for Viruses on the Tree of Life, Frontiers in Microbiology. [22 Jan 2024]

      Related Pages  

• Addy Pross What is Life? How chemistry becomes biology on this website.

       Further Reading  

• www.chemoton.com website explains what the chemoton theory is, its significance, chemical and biological results, list of publications and curriculum vitae of Tibor Gánti. The complete site is available as an 18 page pdf document. So there is a lot to learn about Gánit's theory for those unable to buy the book. [14 Mar 2004] This website is considerable expanded. See for example the obituary (2009). [15 Jul 2014]
• email from Gánti, 18 Jan 2004.
• The Chemoton model at wikipedia.
• Robert Rosen (1991) Life Itself: A Comprehensive Inquiry into the Nature, Origin, and Fabrication of Life, Columbia University Press, Info. "Rosen argues that reductionism does not work in biology and ignores the complexity of organisms." See more details: wikipedia page.
• 'The NASA defintion of life': A committee assembled in 1994 by NASA proposed that life is a "self-sustaining chemical system capable of Darwinian evolution." following a suggestion by Carl Sagan. Joyce G.F. Deamer D.W. Fleischaker G. (1994) Origins of Life: The Central Concepts. Jones and Bartlett. Foreword.
• M. Rizzotti (1996) (ed) Defining Life. The central problem in theoretical biology. University of Padova. Contributions by Brack, Cela-Conde, Colombo, Fox, Gaeta, Gánti, Hartman, Igamberdiev, Lazcano, Luisi, Nakamura, Omodeo, Varela. I fully agree with the idea expressed in the title of the book: defining Life is the central problem in theoretical biology and 'philosophy of biology'.
• James Randerson (2004) "Life began with a knack for copying", New Scientist 22 May 2004, p. 15. Very interesting! "The essence of life is replication, everything else is subordinate. Metabolism is simply an adaptation to aid replication." Based on a publication of Addy Pross in Origins of Life and Evolution of the Biosphere, vol 34, p.307-321. Abstract. Here is a 4-page summary of his argument.
• Dirk Schulze-Makuch, Louis N. Irwin (2004) Life in Universe. Expectations and Constraints. Springer, 172 pages. Important for the definition of life. Now also in paperback (see above).
• Eric D. Schneider & Dorion Sagan (2005) Into the Cool: Energy Flow, Thermodynamics and Life, University of Chicago Press, 362 pp. They claim that non-equilibrium thermodynamics explains the origin of life. There is an expert review of the book by Doyne Farmer in Nature of 4 Aug 2005 pp 627-628.
• Gert Korthof (2006) Similarities and Dissimilarities of Computer Viruses and Biological Viruses.
• Tree of Life Web Project.
• Carl Zimmer (2006) Did DNA Come From Viruses? Science 12 May 2006 VOL 312 870-872 Research that began with a study of replication enzymes used by bacteria has led to a controversial theory: Viruses may have helped shape all three major domains of life. (Patrick Forterre).
• Martin A. Nowak and Hisashi Ohtsuki (2008) 'Prevolutionary dynamics and the origin of evolution', PNAS September 30, 2008; 105 (39).
  • "We have proposed a mathematical theory for studying the origin of evolution". "Life is that which replicates and evolves. The origin of life is also the origin of evolution. A fundamental question is when do chemical kinetics become evolutionary dynamics?". "The defining feature of biological systems is evolution. Biological organisms are products of evolutionary processes and capable of undergoing further evolution." According to Ganti the potential to evolve is not an absolute, but a potential life criterion (B2). "Evolution needs a generative system that can produce unlimited information. Evolution needs populations of information carriers. Evolution needs mutation and selection. Normally, one thinks of these properties as being derivative of replication, but here, we formulate a generative chemistry ('prelife') that is capable of selection and mutation before replication." That is new. "Selection emerges in prelife, if different reactions occur at different rates". "In our theory, natural selection is not a consequence of replication, but instead natural selection leads to replication." This is a new and original theory, but I cannot follow the mathematics.
• Michel Morange (2008) 'Life Explained' Yale University Press, Hardcover, 224 pages.
  • "In this accessible and fascinating book, Michel Morange draws on recent advances in molecular genetics, evolutionary biology, astrobiology, and other disciplines to find today's answers to the question of life." Michel Morange is de author of A History of Molecular Biology, and The Misunderstood Gene. 15 Nov 2008
• Steen Rasmussen, Mark A. Bedau, Liaohai Chen, David Deamer, David C. Krakauer, Norman H. Packard and Peter F. Stadler. (2008) Protocells. Bridging Nonliving and Living Matter. 2008. MIT Press.
  • "Protocells offers a comprehensive resource on current attempts to create simple forms of life from scratch in the laboratory. These minimal versions of cells, known as protocells, are entities with lifelike properties created from nonliving materials, and the book provides in-depth investigations of processes at the interface between nonliving and living matter."
• Steven A. Benner (2010) Defining Life, Astrobiology, Dec 2010. (free)
  • "Any definition is intricately connected to a theory that gives it meaning. Accordingly, this article discusses various definitions of life held in the astrobiology community by considering their connected "theories of life.""
• Mark A. Bedau, Carol E. Cleland (eds) (2010) The Nature of Life: Classical and Contemporary Perspectives from Philosophy. Cambridge University Press. Mark A. Bedau is an American philosopher who works in the field of Artificial Life. Carol E. Cleland is Professor of Philosophy, and is writing her next book The Quest for a Universal Theory of Life: Searching for life as we don't know it.
• Stuart A. Kauffman (2011) Approaches to the Origin of Life on Earth, Life 2011, 1(1), 34-48; free full text:
  • "To his credit, Ganti was the first to bring together in one picture a minimal model of what would later be seen as satisfying at least minimal requirements for protolife."
• David L. Abel & Kirk K. Durston (2011) The First Gene: The Birth of Programming, Messaging and Formal Control, LongView Press. There is a discussion of the chemoton model in chapter 9.4.5: "Tibor Ganti's well-developed chemoton model".
• Terrence W. Deacon (2011) Incomplete Nature: How Mind Emerged from Matter, W. W. Norton & Company, 624 pages. (about the definition of life, orgin of life and much more). See review of the book: ACHING VOIDS AND MAKING VOIDS by Daniel C. Dennett, The Quarterly Review of Biology, December 2013
• K. Chodasewicz (2014) Evolution, reproduction and definition of life Theory Biosci. 133(1):39-45. Epub 2013 May 15.
• Addy Pross (2012) What is Life? How chemistry becomes biology, Oxford University Press, 224 pages. Pross is a theoretical chemist. See my review of his book. Pross mentions Gánti in passing, but he he thinks that membranes are later evolutionary additions.
• Gert Korthof (2013) New Szostak protocell is closest approximation to origin of life and Darwinian evolution so far (13 Dec 2013)
• This is how the free online Stanford Encyclopedia of Philosophy defines 'Life' (Tibor Gánti is absent).
• Ewen Callaway: 'Minimal' cell raises stakes in race to harness synthetic life, Nature 24 Mar 2016. "Genomics entrepreneur Craig Venter has created a synthetic cell that contains the smallest genome of any known, independent organism. Functioning with 473 genes, the cell is a milestone in his team's 20–year quest to reduce life to its bare essentials and, by extension, to design life from scratch."
• Gert Korthof (2020) The difference between physics and biology was published on my blog on 14 August 2020.
• Tibor Gánti is discussed in this blog: Did Nick Lane solve the origin of life? 5 sep 2022.

• Gert Korthof (2013) Het ontstaan van het leven en de zin van het leven, korthof.blogspot 12 december 2013.
• Gert Korthof (2014) Een nieuwe definitie voor 'leven' 15 jul 2014. Shows that new research changes our view of viruses so that they can be included in Ganti's definition of life.