2011 2012 JBSD Def Life

259
Journal of Biomolecular Structure &

Dynamics, ISSN 0739-1102
Volume 29, Issue Number 2, (2011)
Adenine Press (2011)
Phone: +972 4 828 8096
Fax: +972 4 824 6554
E-mail: trifonov@research.haifa.ac.il
Edward N. Trifonov
1,2
1
Genome Diversity Center, Institute of
Evolution, University of Haifa, Mount
Carmel, Haifa 31905, Israel
2
Department of Functional
Genomics and Proteomics,
Faculty of Science, Masaryk University,
Kotlarska 2, CZ-61137 Brno,
Czech Republic
Vocabulary of Denitions of Life Suggests a Denition
http://www.jbsdonline.com
Abstract
Analysis of the vocabulary of 123 tabulated denitions of life reveals nine groups of den-
ing terms (denientia) of which the groups (self-)reproduction and evolution (variation)
appear as the minimal set for a concise and inclusive denition: Life is self-reproduction
with variations.
Key words: Consensus; Denientia; Evolution; Origin of life; Self-reproduction; Variations;
Vocabulary.
Over 100 of denitions of life exist today (1, 2) learned opinions each one of
which is, or has been in the past, defended not without a reason though generally
met with skepticism. The skepticism is multiplied by the above number, leaving
almost no chance for new formulations which, however, continue to appear. An
excellent overview of the current status of the problem is given by a special issue
of the journal Origins of Life and Evolution of Biospheres (3). Sixteen papers of
this issue, expert opinions, display a variety of philosophical and historical aspects
of dening life, and inevitable limitations of about every approach and view point.
The denitions are more than often in conict with one another. Undeniably, how-
ever, most of them do have a point, one or another or several, and common sense
suggests that, probably, one could arrive to a consensus, if only the authors, some
two centuries apart from one another, could be brought together. One thing, how-
ever, can be done sort of voting in absentia asking which terms in the denitions
are the most frequent and, thus, perhaps, reecting the most important points shared
by many. Such analysis is offered below, revealing those most frequent terms that
may be used for tentative formulation of the consensus.
In the Table I the vocabulary of words used in 60-denition set of Barbieri (1)
and 90-denition collection of Popa (2) is presented. The non-redundant total size
of two collections is 123 denitions. All words of 3 or more letters are taken for
the survey, excluding connective ones (the, and, that, etc.). The words that
appear more than 4 times in the collections are presented in the Table I (the full
list is available by request). The life, as deniendum, is at the top of the list.
Inspection of the list reveals that amongst frequent words the ones closely related
to, e.g., life group (such as living, alive) appear as well. This suggests
combination of various words in groups by their common meaning. The Table II
displays several such groups, topmost by their scores. Words of each group are
present in at least 30% of the denitions analyzed. The groups of smaller size
(not shown) contain, essentially, only words with the same root (e.g., denition,
dened, dening, etc.).
Open Access Article
The authors, the publisher, and the right
holders grant the right to use, reproduce,
and disseminate the work in digital form
to all users.
260
Trifonov
Table I
List of most frequent words in the denitions of life.
Life 123 Organic 11 Internal 7 Capacity 5
Living 47 Alive 10 Replication 7 Different 5
System 43 Evolution 10 Being 6 Force 5
Matter 25 Materials 10 Change 6 Form 5
Systems 22 Reproduction 10 Characteristics 6 Functional 5
Environment 20 Existence 9 Entity 6 Highly 5
Energy 18 Dened 8 External 6 More 5
Chemical 17 Growth 8 Means 6 Mutation 5
Process 15 Information 8 Molecules 6 Necessary 5
Metabolism 14 Open 8 One 6 Network 5
Organism 14 Processes 8 Order 6 Objects 5
Organization 14 Properties 8 Organisms 6 Only 5
Complexity 13 Property 8 State 6 Organized 5
Ability 12 Reproduce 8 Things 6 Reactions 5
Itself 12 Through 8 Time 6 Self-reproduction 5
Able 11 Complex 7 Way 6 Some 5
Capable 11 Evolve 7 Based 5 Three 5
Denition 11 Genetic 7 Biological 5
Thus, the consensus of the life denition patched from these nine denientia would
be: Life is [System, Matter, Chemical (Metabolism), Complexity (Information),
(Self-)Reproduction, Evolution (Change), Environment, Energy, Ability,] where
the square brackets correspond to some compact expression containing the words
listed within. For example, one possibility is:
Life is metabolizing material informational system with
ability of self-reproduction with changes (evolution),
which requires energy and suitable environment. [1]
Since the analysis described, inevitably, is not free from some arbitrariness in
assignment of the words to this or another group, it would be desirable to compare
it to a similar study conducted by an independent laboratory. The work of Kompan-
ichenko (4) offers such independent analysis. In that work the denitions of life are
taken from the collection of papers and denitions (5) that preceded the publication
of Popa (2). Kompanichenko considered denitions given by 63 authors from the
book of Palyi et al. (5), and extracted from the denitions 19 major unique funda-
mental properties of biological systems. Instead of words the notions of the prop-
erties have been used, often expressed by several words, differently by different
authors. The largest category, according to Kompanichenko, is Capable of evolu-
tion including the increase of complexity, hierarchy and the display of self-perfecting
logic (close to Evolution in our list) 32 authors. The fundamental property
Capability for self-reproduction (Reproduction in our list) has been mentioned
by 27 authors. Another fundamental property, Capability for self-replication
(11 authors) also would go to Reproduction group, 38 authors together. Note that
according to the notion count of Kompanichenko our categories Evolution and
Reproduction appear at the top of the list, while by word count (this work) they
rank more modestly. Then follow Performance and control of metabolism, includ-
ing autocatalysis, cyclic chemical processes, feedback loops, and active transport
(Chemical of our list) 25 authors, Ability to extract (free) energy and matter
from the environment (Energy, Matter, Environment, and Ability in our
list) 16 authors, and Capacity to accumulate, re-organize and transmit genetic
information (Complexity/Information) in our list) 13 authors. Remaining
13 properties considered by Kompanichenko are mentioned by smaller number of
authors (1 to 7) and are not reected in our list of major terms. This approach, obvi-
ously, is not free from subjective assignments as well. It is remarkable, however,
that eight of nine categories of our list of major terms are also at the top of the list
of Kompanichenko.
261
Defnition of Life
Although the extract [1] above may already appear as a reasonable denition, one,
of course, would like to have it more concise, and desirably, containing compo-
nents that are both necessary and sufcient, either alone or in combination. The
possible shorter denitions would be, of course, subject of a thorough evaluation,
inviting new discussions of the denition problem, but on a new basis of limited
number of relevant terms. Below one rather plausible reduction is suggested. First,
some of these consensus terms implicitly involve others. For example, existence of
metabolism implies both energy and material supply which also represent environ-
ment. Self-reproduction (replication) appears to be the most inclusive term of the
nine groups above, as it implies metabolism and system as well. That is, if the self-
reproduction is going on, it can proceed only on condition that metabolism, system,
energy and material supply are also in place. The complexity (information) can be
considered also as product of self-reproduction with changes (evolution), on the
evolutionary route from simple to complex. We are, thus, left with two indepen-
dent notions: self-reproduction and changes (evolution). None of these two implies
another one. They, actually, exclude one another, as self-reproduction is exact copy-
ing, no changes, while changes can not relate to exact copying. These two notions can
be combined in a third one: an almost exact self-reproduction or self-reproduction
with variations, suggesting, thus, a tentative minimalistic denition.
Evolution (and natural selection) means changing inheritance, that is, causing vari-
ations in self-reproduction. As it has been said by Darwin (6): if variations
useful to any organic being ever do occur, assuredly individuals thus charac-
terized will have the best chance of being preserved in the struggle for life; and
from the strong principle of inheritance, these will tend to produce offspring
Table II
Groups of words with similar meaning.
LIFE 123 COMPLEXITY 13
living 47 information 8
alive 10 complex 7
being 6 other related words 46
biological 5 Sum 74
other related words 8 REPRODUCTION 10
Sum 199 reproduce 8
SYSTEM 43 replication 7
systems 22 self-reproduction 5
organization 14 other related words 33
organism 14 Sum 63
order 6 EVOLUTION 10
organisms 6 evolve 7
network 5 change 6
organized 5 mutation 5
other related words 40 other related words 20
Sum 155 Sum 48
MATTER 25 ENVIRONMENT 20
organic 11 external 6
materials 10 other related words 15
molecules 6 Sum 41
other related words 36 ENERGY 18
Sum 88 force 5
CHEMICAL 17 other related words 17
process 15 Sum 40
metabolism 14 ABILITY 12
processes 8 able 11
reactions 5 capable 11
other related words 26 capacity 5
Sum 85 other related words 1
Sum 40
262
Trifonov
similarly characterized (6, Chapter 4, italics by ENT). The denition of life based
on only two terms extracted from the vocabulary of denitions, and consistent with
Darwins views would be, thus:
Life is self-reproduction with variations. [2]
Here the tandem self-reproduction with variations should be considered as one
indivisible term of very clear Darwinian meaning. Of 123 different denitions only
18 contain this pair of denientia, in combination with other dening terms of the
Table II. The most succinct among them is one by Oparin (7):
Any system capable of replication and mutation is alive.
The vocabulary approach implemented in this work is conceptually close to the
Principal Component Analysis (8, 9) which is applicable to large ensembles of
quantitative data. The data are reduced to several independent (orthogonal) com-
ponents, and the major principal component is extracted that covers most of the
data. Similarly, our vocabulary of denitions is reduced to several groups of words
with different meaning. The same procedure of extraction of a single principal
component has been used in derivation of consensus temporal order of engage-
ment of amino acids in early evolution (10, 11). The order has been established as
a consensus of a large number of rather different chronologies suggested by vari-
ous authors. As this order correlates well with thermostability of respective codon-
anticodon pairs, the reconstruction of the Evolutionary Chart of Codons became
possible. From the properties of the Chart several important features of the earli-
est stages of molecular evolution have been predicted, and conrmed by sequence
analyses (12, 13). The earliest steps of the evolution of the codons also suggested
two major stages in the origin of life self-reproduction (exact replication of the
ideal RNA duplex in the above theory, one strand of which is repeating triplet GCC
n
,
while another strand is complementary GGC
n
), and variations (appearance of point-
mutated versions of GCC and GGC in the subsequent replications). That ended
logically in the denition of life self-reproduction with variations (14), identical
to above [2]. In its earlier version almost precise replication it appeared in the
collection of denitions of life gathered by Barbieri (1). (That formula has been
excluded from the analysis above and did not enter the vocabulary).
According to this model-based denition, any experimental work involving the
GCC
n
* GGC
n
replicator would border the life-nonlife transition. The denition of
life, thus, is naturally required for the exploration, at least as a practical guide in the
research (15). Thus, it is not purely philosophical and historical matter anymore. This
was one of the motivations for the linguistic analysis described in the paper. The
derived denition [2] is minimalistic both by denientia involved and, independently,
by structurally minimal size of the presumed earliest replicator to which the denition
fully applies (14).
One unforeseen property of the minimalistic denition is its generality. It can be
considered as applicable not just to earthly life but to any forms of life imagi-
nation may offer, like extraterrestrial life, alternative chemistry forms, computer
models, and abstract forms. It suggests a unique common basis for the variety of
lives: all is life that copies itself and changes.
One important question to address: is the minimalistic denition both necessary
and sufcient? Even most primitive forms of observable life are still too complex,
to claim that they can be reduced to the above simple formula. The applicability of
the denition can only be tested on much simpler articial life-like models which
one day will, hopefully, be designed and brought to life, by providing articially
263
Defnition of Life
produced necessary ingredients. This day is not far away. A self-catalytic gen-
eration (cross-replication) of plus-strand and minus-strand ribozymes from their
constituent 14-mer and 52-mer RNA chains has been recently accomplished (16).
The system also allows to introduce and to monitor evolutionary changes in the
ribozymes. It does not include, though, the elementary template polymerization
steps one would expect the simplest self-reproducing system to have. The experi-
mental chemical template polymerization has been intensively studied during last
two decades (for most recent review see (17)). An efcient complementary primer
extension on C
15
template has been achieved in protocells by using chemical
RNA analog (18). No evolutionary changes have been observed so far in the sys-
tem. Yet simpler setup, with oligo-riboA in aqueous solution has been developed,
in which the chain of RNA could elongate indenitely, apparently, due to forma-
tion of complementary contacts between polyA chains (19). In this work similar
extension of oligoG ligated to oligoC has been observed as well, with incorporation
of complementary Gs. Creation of a bacterial cell with chemically synthesized
genome (20) has to be mentioned as another case of a system at the border life-
non-life. This is, actually, a very large scale bacterial transformation where the
transforming DNA has been, indeed, chemically synthesized according to natural
design previously fully sequenced genome, with some changes. The synthesized
genome did replicate many rounds. However, it should be considered as very much
assisted replication as it was provided with an initial natural cytoplasm. No evo-
lutionary changes in the design have been monitored. Nearly fully articial life
with the properties described by the above minimalistic denition has been created
many years earlier, by Sol Spiegelman his famous monster of replicating degen-
erate products of mutating Q-beta RNA. The monster RNA versions have practi-
cally lost any sequence similarity to their viral ancestor, in the process of ingenious
evolutionary game (21). This has been an assisted replication as well, since the
experiments have been performed in presence of natural replicase. However, this
protocol is, probably, the most promising starting model for eventual design of
simplest truly articial life, since for modern peptide chemistry the synthesis of an
active analog of the replicase, perhaps, is as plausible as the chemically synthesized
genome.
Acknowledgements
Author is grateful to anonymous reviewers for thoughtful comments, criticism and
suggestions towards improvement of the paper.
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Date Received: March 17, 2011
Communicated by the Editor Ramaswamy H. Sarma
265
Defnition of Life
Appendix
Full list of the words making groups of the Table II.
LIFE 123 polymer 1
living 47 polypeptides 1
alive 10 polysaccharides 1
being 6 protein 1
biological 5 proteinaceous 1
animate 4 substances 1
beings 3 water 1
animated 1 Sum 88
Sum 199 CHEMICAL 17
SYSTEM 43 process 15
systems 22 metabolism 14
organization 14 processes 8
organism 14 reactions 5
order 6 molecular 4
organisms 6 production 3
network 5 metabolic 2
organized 5 metabolize 2
assembly 3 chemistry 2
building 3 produces 2
components 3 decay 1
composed 3 degradable 1
ensemble 3 degradation 1
aggregates 2 exchange 1
automata 2 precursors 1
consists 2 processing 1
ordered 2 produced 1
arrangement 1 regeneration 1
automaton 1 reparation 1
automatons 1 synthesis 1
biosystem 1 synthesize 1
built 1 Sum 85
consisting 1 COMPLEXITY 13
contain 1 information 8
containing 1 complex 7
ensembles 1 code 4
multilevel 1 entropy 3
networks 1 knowledge 3
orderly 1 patterns 3
organizational 1 communicate 2
organize 1 molecular-informational 2
rearrangement 1 pattern 2
self-organization 1 program 2
self-organized 1 reading 2
Sum 155 algorithmic 1
MATTER 25 complicated 1
organic 11 computational 1
materials 10 digital 1
molecules 6 feedback 1
material 4 feedbacks 1
compounds 3 feedback-loops 1
nucleic 3 informational 1
polymers 3 informationally 1
proteins 2 informationally-controlled 1
acids 2 information-storage 1
uid 2 instructional 1
substance 2 instructions 1
acid 1 low-entropy 1
aqueous 1 maximally-complex 1
bioelements 1 message 1
carbon 1 program-controlled 1
carbon-based 1 programs 1
molecule 1 self-correction 1
monomers 1 self-instruction 1
oligosaccharides 1 self-reading 1
(Continued)
266
Trifonov
sequence 1 mutability 1
signal 1 modies 1
Sum 74 mutandis 1
REPRODUCTION 10 mutations 1
reproduce 8 mutatis 1
replication 7 variant 1
self-reproduction 5 Sum 48
self-replication 3 ENVIRONMENT 20
autopoiesis 2 external 6
autopoietic 2 conditions 3
multiplication 2 surroundings 3
proliferation 2 biosphere 1
replicate 2 condition 1
self-replicating 2 conditionally 1
self-reproduce 2 conditioned 1
self-reproducing 2 environmental 1
copies 1 environments 1
copying 1 medium 1
perpetuate 1 microenvironment 1
perpetuated 1 supply 1
proliferating 1 Sum 41
recreate 1 ENERGY 18
reproduces 1 force 5
reproducibility 1 thermodynamic 3
reproducing 1 engine 2
self-duplication 1 forces 2
self-generating 1 power 2
self-generation 1 powers 2
self-perpetuating 1 energetically 1
self-producing 1 energy-dependent 1
Sum 63 energies 1
EVOLUTION 10 engines 1
evolve 7 thermodynamical 1
change 6 thermodynamics 1
mutation 5 Sum 40
changes 4 ABILITY 12
evolutionary 2 able 11
mutate 2 capable 11
variation 2 capacity 5
errors 2 capacities 1
evolved 1 Sum 40
evolves 1
Appendix (Continued)
Volume 29, Issue Number 4, February 2012
597
Editorial
A Conversation on Denition of Life
In his letter of submission of the Denition of Life paper (1), Edward Trifonov
indicated
The subject is very much debatable, the analysis may appear to some controver-
sial, and the claim outrageous. That also means, that the paper could be sug-
gested for open discussion. I am ready to confront any challenges.
Well, I thought, let me see what the referees have to say. One referee in part
said:
I happen to disagree with Edward Trifonov, and yet I strongly recommend the
publication of his paper. The reason is that the denition of life is an extremely
important issue but also one where there is virtually no objective approach.
Trifonovs paper is probably the rst of this kind, and it is for that reason that it
should be circulated. When it is published, it shall be possible to discuss it and
eventually propose something better, but there must be a starting point.
Interesting, this referee disagrees with the author, but wants me to publish the paper
to start a Conversation among his peers. Wow! What a magnanimous gesture!
And a second referee in part said:
And indeed, the resulting denition thus laboriously rened from all the pre-
vious ones strikes the reader as very concise and straightforward. I must confess
that my rst reaction to this move by the author was how come nobody thought
about it so far?
All in all, this paper combines a brilliant and rigorous analysis with a profound
scientic and philosophical result. It certainly deserves being published as is
in any leading scientic journal.
Then we heard from referees about the absence of reproducibility, controls, and
the utter lack of the consideration of central elements in life such as beauty,
truth and love, a denition of life devoid of life and soul, manufactured from
linguistics.
I thought that the effort by Trifonov was an interesting intellectual adventure that
warranted open comments and discussion by scientists and philosophers research-
ing in life, its origins (2-6) and evolution (7-11). So I extended them an invitation
and most of them agreed to provide the comments. Prof. Pier Luigi Luisi did not
write a formal response to Trifonovs paper, but wrote me the letter reproduced
verbatim below:
Dear Rama
I have been thinking about it, and denitely decided not to invest my time to
write an article, as it would be to give relevance to what I consider a poor piece
Corresponding author:
Ramaswamy H. Sarma
Phone: 518-456-9362
Fax: 518-452-4955
E-mail: rhs07@albany.edu
Ramaswamy H. Sarma
Department of Chemistry,
State University of New York at Albany,
Albany NY 12222, USA
598 Sarma
Journal of Biomolecular Structure & Dynamics, Volume 29, Number 4, February 2012
of science-and I do not want to do that. I would like how-
ever to briey explain to you the reasons for my negative
stand.
What Trifonov does, is to make a kind of average of all
possible life denitions of life, giving to everyone the
same statistical weight. A democratic decision. But sci-
ence does not work this way. It comes to my mind the sta-
tistic that some politicians do: given a group of scientists
who says: two and two makes four; and another group who
say: two and two make sixthe politicians say, well, let us
not argue, lets make so that two and two makes ve...
This kind of statistics is simply wrong, non-sense things
should rst be eliminated. Of course this necessitates an
arbitrary act of courage-this is the responsibility of the
scientist.
And then the basic result of our Author, that life is repro-
duction and variation-which means, change, evolution...
my God, we have been debating for so many years that
this is not simply so. The old grand mother of our author is
not capable of reproduction, but is (I hope) still living, and
so are all women of this planet over 60 years. Not able to
reproduce...and then not living? And to decide whether
an oak tree is living, you wait a few hundred years until
it reproduces? Reproduction is important, but it is a con-
sequence of life, it can be there or not, it depends...this is
so obvious, and common sense is much more important
than statistics.
And the confusion with variation-changes, evolution: a
colony of bacteria which is not reproducing in a measur-
able time scale-is not living? and again, to decide whether
something is living you wait until you measure changes?
which kind of?
As I told you, Rama, these issues were already debated
in my old paper (1998) on the denition of life and in my
book on the emergence of life-long ago. Trifonov does
not mention all this, and he is right, in the sense that I am
now completely on another place; let me only add that,
when I read a paper, I always ask myself whether this is
something I would suggest to my students. In this case,
my answer is denitely negative, as they would not learn
anything-they would probably get more confused.
Dear Rama, although my decision is denitive, if you
want/need to use some of the material in this letter, you
can do it, thanks for the trust.
Luigi
References
P. L. Luisi. About various denitions of life. Origins of Life and
Evolution of the Biosphere 28, 613-622 (1998).
P. L. Luisi. The Emergence of Life: From Chemical Origins
to Synthetic Biology, Cambridge Univ. Press, Cambridge UK
(2006).
In my letter of invitation, I made it explicitly clear that their
comments would not be subject to the normal peer review
so that they could express their personal points, views, and
evaluation of Trifonovs paper without interference from the
referees. This is perfectly ne because the comments them-
selves are not research articles which require mandatory peer
evaluations, but just pure comments, and referees inserting
moderation and balance into the comments is not right. These
comments are brief items with a short list of references, and do
not contain original research data. They are essentially open
referee reports. The comments are published without dates
received and without the name of the Communicating Editor
because they are not regular research articles. Finally this
Journal is publishing the section consisting of this editorial,
the 19 comments and the author response as Open Access.
This is because this Journal strongly believes that doctoral
students in biochemistry and molecular biology will benet a
great deal from a study of these comments; and Open Access
publication enables this.
I have received comments from 19 laboratories across the
globe. I thank all of them for reading Trifonovs paper and
expressing their opinion. I am particularly grateful to Nobel
Laureate Jack Szostak for visiting Albany, delivering the
Keynote address at the 17
th
Conversation, and chairing the
session on origin of life there and for participating in this
Conversation.
References
J. W. Szostak. 2. J Biomol Struct Dyn 28, 1059-1059 (2011).
U. J. Meierhenrich, J.-J. Filippi. C. Meinert, J. H. Bredehft, 3.
J.-i. Takahashi, L. Nahon, N. C. Jones, and S. V. Hoffmann. J Biomol
Struct Dyn 28, 1060-1061 (2011).
G. Costanzo, S. Pino, F. Ciciriello, and E. Di Mauro. 4. J Biomol Struct
Dyn 28, 1061-1061 (2011).
J. P. Ferris, P. C. Joshi, M. F. Aldersley, and J. W. Delano. 5. J Biomol
Struct Dyn 28, 1062-1062 (2011).
A. E. Engelhart, R. Buckley, E. D. Horowitz, and N. V. Hud. 6.
J Biomol Struct Dyn 28, 1063-1063 (2011).
W. L. Duax, R. Huether, D. Dziak, and C. McEachon. 7. J Biomol Struct
Dyn 28, 1066-1067 (2011).
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Dyn 28, 1068-1068 (2011).
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D. M. Schneider, and E. ONeill. J Biomol Struct Dyn 28, 1071-1072
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T. J. Glembo and S. B. Ozkan. 10. J Biomol Struct Dyn 28, 1068-1069
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A. Goncearenco and I. N. Berezovsky. 11. J Biomol Struct Dyn 28,
1065-1065 (2011).
599
Comment
Attempts to Dene Life Do Not Help to Understand
the Origin of Life
Attempts to dene life are irrelevant to scientic efforts to understand the origin
of life. Why is this? Simply put, the study of the origin of life is an effort to
understand the transition from chemistry to biology. This fundamental transition
was the result of a lengthy pathway consisting of many stages, each of which is
the subject of numerous scientic questions. Simple chemistry in diverse environ-
ments on the early earth led to the emergence of ever more complex chemistry
and ultimately to the synthesis of the critical biological building blocks. At some
point, the assembly of these materials into primitive cells enabled the emergence of
Darwinian evolutionary behavior, followed by the gradual evolution of more com-
plex life forms leading to modern life. Somewhere in this grand process, this series
of transitions from the clearly physical and chemical to the clearly biological, it is
tempting to draw a line that divides the non-living from the living. But the location
of any such dividing line is arbitrary, and there is no agreement on where it should
be drawn. An inordinate amount of effort has been spent over the decades in futile
attempts to dene life often and indeed usually biased by the research focus
of the person doing the dening. As a result, people who study different aspects
of physics, chemistry and biology will draw the line between life and non-life at
different positions. Some will say there is no life until a well dened set of meta-
bolic reactions are in place. Others will focus on spatial compartmentalization, on
the various requirements for Darwinian evolution, or on the specic molecules of
inheritance. None of this matters, however, in terms of the fundamental scientic
questions concerning the transitions leading from chemistry to biology the true
unknowns and subject of origin-of-life studies.
Beyond the arbitrary nature of efforts to dene the boundary between non-life
and life, this effort is illusory for a deeper reason. As one focuses experimentally
on any of the dening properties of life, the sharp boundary seems to blur,
splitting into ner and ner sub-divisions. As an example, let us look at the emer-
gence of Darwinian evolution, which is often cited [e.g., see Table II, in ref. 1]
as a key aspect of the denition of life (with good reason, as Darwinian evolu-
tion is indeed the unifying characteristic of all of biology). Certainly once cells
with genetically encoded advantageous functions existed, classically dened
Darwinian evolution had begun, and most people would dene such cells as alive.
But what about the previous steps? Such cells would likely have been preceded by
protocells, with replicating genetic information, but lacking coded functions that
provided a cellular advantage. At this stage, replication with heritable variation
would have existed, and whatever process drove replication would most likely
have had biases that led to changes in the genetic structure of the population over
time. Would that minimalist form of evolution qualify such protocells as being
alive? Going back even further, consider genetic molecules replicating in solution
Jack W. Szostak
E-mail: szostak@molbio.mgh.harvard.edu
Jack W. Szostak
Howard Hughes Medical Institute and
Department of Molecular Biology and
Center for Computational and
Integrative Biology, Massachusetts
General Hospital, 185 Cambridge Street,
Boston, Massachusetts 02114
600 Szostak
or on particulate surfaces again, biases in replication would
lead to selection for sequences that are better templates, i.e.,
easier to replicate. Even the assembly of the rst genetic
polymers would have had biases, leading to non-random
population structures. Darwinian evolution itself emerged in a
series of stages, step-by-step, gradually leading to the almost
innite potential for organismal variation seen in modern
biology. And yet, to dene a single point along the progres-
sion as the point at which Darwinian evolution rst emerged
would be difcult. More importantly, such a denition would
not further our understanding of the transitions involved or
the nature of the physical and chemical forces driving those
transitions.
What is important in the origin of life eld is understanding
the transitions that led from chemistry to biology. So far, I
have not seen that efforts to dene life have contributed at all
to that understanding.
Acknowledgement
I thank Noam Prywes and Aaron Englehart for helpful
comments on this manuscript.
Reference
601
Comment
Trifonovs Meta-Denition of Life
What is a Denition in the Realm of Biology?
The problem of denition is at the basis of the problem of understanding. Any level of
understanding of any natural phenomenon or object entails its description, followed
by the comparison (in our brain or in the pages of an Herbarium, or by a computer
program) with similar phenomena or objects. Between comparison and understand-
ing we encounter classication. The problem of classication is not solved.
The tradition we are acquainted with is the Linnaean System. Simplifying
(too much, I am afraid), according to this system every organism belongs to a
Species and to a Genus. The properties allowing the organism to be encased in
a Species are, in semiological terms, Dictionarian (that is: context-free). The
characters for the Genus are Encyclopaedian (context-dependent). Given that
the two categories are based on principles that do not belong to the same category,
in terms of logics the System is ambiguous. Linnaean classication has had some
use essentially because it empirically approximates the deniendum to the closest
functional happenstance. The upper oors of the System (Families, etc.) suffer
from the same approximation. Similar ambiguities characterize other Systems.
Aristotelian classication was, in spite of its almost bi-millennial life, even more
logically ill-based. To the point that when a careful analysis was made, it was
recognized by Porrius that applying its principles with some rigour one would
quickly hit the limit set by penuria nominum, scarcity of names, impossibility to
classify providing the appropriate labels.
The era of genomics has claried this point with precision. Each genome is itself:
similarities abound, as differences do. The basic structural, functional and infor-
mational principles of living entities are the same since the very beginning of their
history.
These principles essentially consist of the organization of a genotype (the egg)
gathering, maintaining and transmitting information related to itself and to a phe-
notype (the chicken), harnessing and directing energy and matter into the further
organization, maintenance and transmission of the egg. From the earliest infor-
mation to the extant enormous (and informationally limitless) genomes no inter-
ruption exists (by denition), no rm border can be traced. Shufing genes from
one genome to others, constructing genetic chimaeras made of genes originated
in different Kingdoms or, simply, just performing meta-genomics of asks of
sea water shows the principle of penuria nominum in contemporary terms. In the
realm of biology there are no barriers, denitions are elusive.
Thats where Trifonovs thought comes into play.
Ernesto Di Mauro
Phone: +39.06.4991.2880
Fax: +39.06.49912500
E-mail: ernesto.dimauro@uniroma1.it
Ernesto Di Mauro
Dept. of Biology and Biotechnologies
Charles Darwin University
Sapienza, P.le Aldo Moro, 5, 00185
Roma, Italy
602 Di Mauro
A Radical Approach
The contribution of this paper is in its hidden radical criti-
cism, and in the solution it proposes.
My personal opinion is that no acceptable denition of life
exists, yet. According to the most popular one, life is a self-
sustained chemical system capable of undergoing Darwinian
evolution (2). This is very close to the denition provided
by Oparin: Any system capable of replication and mutation
is alive (3). However, life is a process, not a system. In addi-
tion, if a denition relies on the variation (evolution) of its
deniendum, it is intrinsically a description, more than a de-
nition. This does not diminish its empirical value, in a sense
very close to what we have mentioned about the purport of
the Linnaean classication System. Rather, these two deni-
tions help to make the point: we are dealing with descrip-
tions, not denitions.
Trifonovs title implies exactly this: all denitions are relative.
Corollary: a relative denition is not a denition. In a given
frame of reference a law is absolute, or is not. Comparing
the proposed denitions, as he does, is extremely useful (and
original). Especially so if done with the rigour and the wide-
angle that characterize his Gnomic (4) approach. What turns
out is that comparing the denition distilled from his reported
tabulation of the 123 denitions analyzed (namely: life is
self-reproduction with variations) with the currently most
accepted life is a self-sustained chemical system capable of
undergoing Darwinian evolution, the only common term is
self . Which may well be the nal minimalist denition of
life, encompassing them all.
A Way Out from Ambiguity
The difference between description and denition is not just
semantics, is categorical. May the two categories be recon-
ciled? Trifonovs reasoning provides a solution: at the cross
between the two lays, in the realm of biology, Darwins
warm little pond (5). There is where it is believed that every-
thing started, where the rst molecules began accumulating,
replicating and evolving information. His three decades-long
Gnomic approach consists of the compilation and analytical
comparison of essentially all that is known about sequences
(nucleic acids, proteins and, in between, coding functions)
looking for the very rst principles. Gnomic is description
aiming to denition.
I believe that he has come very close to the solution: The
earliest steps of the evolution of the codons also suggested
two major stages in the origin of life self-reproduction (exact
replication of the ideal RNA duplex in the above theory,
one strand of which is repeating triplet GCCn, while another
strand is complementary GGCn), and variations (appearance
of point-mutated versions of GCC and GGC in the subse-
quent replications). (1, and references therein). Accord-
ingly, studies involving the GCCn
*
GGC
n
replicator border the
life-non life transition (6), reducing it to initial experimental
analysis (7). The identication of plausible rst replicators
would help to pinpoint the events that lead from dis-order to
order, and ignite the process that we are struggling to dene,
the rst selves.
I thank E. N. Trifonov for bringing up the important and often
overlooked denition in reference 3.
References
J. Joyce. in D. W. Deamer and G. R. Fleischaker (Eds.), the foreword 2.
of Origins of Life: The Central Concepts, Jones and Bartlett,
Boston (1994).
A. I. Oparin. as referred to in: R. Popa. In Between Necessity and 3.
Probability: Searching for the Denition and Origin of Life. Series:
Adv Astrobiol Biogeophys, Springer, NY, pp. 197-205 (2004).
E. N. Trifonov and V. Brendel. 4. GnomicA Dictionary of Genetic
Codes (1986), VCH. Balaban Publ., Weinheim, Germany.
C. Darwin. The life and letters of Charles Darwin (1888); Vol. 3, 5.
p. 18. Letter to Joseph Hooker. John Murray, London.
E. N. Trifonov. 6. J Cosmology 10, 3374-3380 (2010).
S. Pino, E. N. Trifonov, and E. Di Mauro. 7. Genomics, Proteomics and
Bioinformatics 9, 7-14 (2011).
603
Comment
Dening Life: An Exercise in Semantics or A Route
to Biological Insights?
Asking What is X? questions is a natural human inclination, and because all
scientists that have so far published are undoubtedly human, they discuss such
issues often enough. What is Life? almost by denition is the king of such ques-
tions as far as Biology is concerned (1). Indeed, in the article which I address in
this commentary (2), Edward Trifonov cites a recent special issue of the jour-
nal Origins of Life and Evolution of Biospheres that consists of 16 articles fully
dedicated to different aspects of dening Life and the features of the resulting
denitions (3). Certainly, this is evidence of considerable attention to the subject.
Yet, in itself the question What is Life? hardly can be considered scientic.
Falsication is impossible: whenever one nds an apparent counterexample, i.e. an
entity that possesses all attributes included in the given denition that, however, is
clearly not alive or conversely, an entity that lacks some of those attributes but
is obviously a life form, some kind of intuitive understanding of the living state
superseding any denition is involved. Even corroboration of a denition of life
that would involve nding more and more diverse entities tting the denition is
compromised by the same problem: to count a case as supportive, an independent
criterion is required, but this can only be intuitive.
So we seem to know it when we see it but dening life is an elusive goal and
apparently an inherently meta-scientic (metaphysical) task. The metaphysical
character of the quest for the best denition of life does not necessarily imply
that the exercise is futile. On the contrary, it is easy to envisage at least two areas
of utility for such denitions: didactic better teaching of the fundamentals of
biology and heuristic formulation of new falsiable hypotheses and perhaps
identication and study of novel life forms. I will not address the didactic aspect
here but will briey discuss the potential heuristic power of life denitions after
rst commenting on Trifonovs approach and conclusions.
Trifonov goes about the derivation of a consensus denition of life in a manner that is
unusual in scientic treatises but that has served him fairly well in previous work on
the order of appearance of codons in the genetic code (4). The approach consists in
compiling as many (supposedly) independent denitions as possible and then com-
paring vocabularies of these denitions to derive a consensus, the essential core
that in itself may be hoped to provide for a better (the best) denition. There is no
genuine scientic justication behind this approach and no guarantee that the numer-
ous compared denitions are not all based on common misconceptions. In part, this
indeed could be the case. Trifonovs core/consensus, additionally reduced through
elucidation of apparent dependencies between some of the core terms, provides for a
sensible, intuitively plausible minimalist denition: almost exact self-reproduction
or self-reproduction with variations (2). It is certainly interesting, as Trifonov points
Eugene V. Koonin
E-mail: koonin@ncbi.nlm.nih.gov
Eugene V. Koonin
1
1
National Center for
Biotechnology Information,
National Library of Medicine,
National Institute of Health,
Bethesda, MD 20894
604 Koonin
out, that this objectively derived minimalist denition of life
almost exactly matches the denition given about 50 years by
none other than Alexander Ivanovich Oparin, the famous even
if notorious Russian biochemist who propounded the rst con-
crete physico-chemical scenario for the origin of life.
Yet, all its simplicity and appeal notwithstanding, the mini-
malist denition appears to be neither necessary nor sufcient,
not even internally consistent. A simple implication of infor-
mation theory (and more fundamentally, thermodynamics)
is that error-free replication (more precisely, any informa-
tion transmission process) is impossible (5). Hence the
phrase self-reproduction with variation is actually redundant
because any replication process will be characterized by some
intrinsic error rate. The problem is exactly the opposite: it
has been shown by Eigen and others that for stable informa-
tion transfer (inheritance) down the chain of generations to
be sustained, the error rate must not exceed a certain critical
value known as error catastrophe or mutational meltdown
threshold (6, 7). Thus, a necessary condition for life to evolve
is not simply replication and not replication with variation
(a tautology) but replication with an error rate below the
sustainability threshold (Trifonovs almost exact self-
reproduction ts the bill but appears imprecise). Another
feature of a self-reproducing system that appears necessary
for evolution is the phenotype-genotype feedback, or more
precisely, differential effect of errors on the replication rate.
Such differential tness effect of mutations is a necessary
condition of selection, both in its purifying and positive
(Darwinian) incarnations. Hence replication with an error
rate below the sustainability threshold, with non-uniformly
distributed tness effects of errors could be a candidate for a
necessary and sufcient denition of life, or probably more
precisely, a criterion for identication of life forms (5).
Both Trifonovs consensus denition and the amended one
given here are strictly informational. Any biologist will imme-
diately feel that something is missing in these denitions.
In broad outline, these missing components are: i) chemistry
(metabolism), ii) energy conversion, and iii) structure (vari-
ous forms of compartmentalization); for brevity, these may
be denoted operational components of life forms, in contrast
to informational components (8).
Even more damning for the informational denitions of life, it
may appear that these denitions are easily falsied by com-
puter viruses and all forms of articial life that replicate,
mutate and evolve (9) but arguably are not actual life forms.
However, such falsication is illusory for the simple reason
that these evolving entities themselves are produced by highly
evolved life forms. Clearly, the emergence of such life forms
(and human civilization in particular) was a pre-requisite for
the advent of these replicators they are not life forms as
such but clearly are derived from life forms. We are currently
unaware of life forms evolved from inanimate matter (or so we
believe) that would lack any of the major operational attributes,
in addition to replication. The operational components seem
to be pre-requisite for the evolution of replicators tting the
above criteria, hence the informational denition of life pre-
supposes the existence of some forms of metabolism, energy
transformation and compartmentalization. However, all life
forms on earth, with the exception of viruses which are obligate
intracellular parasites, encompass a much stronger connection
between replication, chemistry, energy and structure: the repli-
cating moiety (genome) encodes key information on the opera-
tional components (primarily in the form of proteins).
Is encoding operational components in the genome a necessary
attribute of life? This does not appear certain at all, and here
we come to the potential heuristic value of life denitions. Let
us formulate a hypothesis: there are purely informational life
forms in which genomes carry only the minimal information
required for replication whereas all operational components
are supplied by the (conducive) environment. Actually, hypo-
thetical information-only replicators are among the essential
features of several origin of life scenarios because emergence
of complex genomes encoding operational components prior to
the advent of an efcient replication mechanism appears effec-
tively impossible (5, 10). This hypothesis may be hard to falsify
but it certainly can be corroborated under two types of settings:
in the laboratory and in extraterrestrial biospheres if and when
such are discovered. Exploration of putative life outside earth
belongs in the future but vigorous attempts to create in the
laboratory an evolving system of replicators employing exog-
enous supplies chemicals and energy are underway, and certain
progress has been achieved with ribozyme polymerases (11).
However, these experimental systems remain a far cry from the
efcient replicators required to start the evolution of life. Thus,
the jury is still out on the information only life hypothesis.
A remarkable feature of all known biological replicators is
their digital character: these replicators are polymers consist-
ing of multiple types of monomers. Such polymers appear
uniquely suited for information encoding, so a plausible
hypothesis seems to be that digital properties are necessary
for life. This hypothesis certainly would be falsied by the
(remarkable) discovery of analog life forms.
To summarize, I believe that the democratic approach
applied by Trifonov to the denition of life problem did not
lead him far astray and converged on a natural and sensible,
if not quite precise, informational denition. In my view,
although life denitions are metaphysical rather than strictly
scientic propositions, they are far from being pointless and
have potential to yield genuine biological insights.
References
E. Schroedinger. What Is Life?: with Mind and Matter and Autobio- 1.
graphical Sketches Cambridge University Press, Cambridge (1992).
Defning Life: An Exercise in Semantics or A Route to Biological Insights? 605
J. Gayon, C. Malaterre, M. Morange, F. Paulin-Cerceau, and S. Tirard. 3.
Origins Life Evol Biospheres 40, 119-244 (2010).
E. V. Koonin. The Logic of Chance: The Nature and Origin of 5.
Biological Evolution FT press, Upper Saddle River, NJ (2011).
M. Eigen. 6. Naturwissenschaften 58, 465-523 (1971).
J. Summers and S. Litwin. 7. J Virol 80, 20-26 (2006).
R. Jain, M. C. Rivera, and J. A. Lake. 8. Proc Natl Acad Sci U S A 96,
3801-3806 (1999).
C. Adami. 9. Nat Rev Genet 7, 109-118 (2006).
E. V. Koonin. 10. Ann N Y Acad Sci 1178, 47-64 (2009).
T. A. Lincoln and G. F. Joyce. 11. Science 323, 1229-1232 (2009).
607
Comment
Merits and Caveats of Using A Vocabulary
Approach to Dene Life
The eld of dening life is rich in artful wording yet lacking in cohesiveness.
Opinions about the necessity and possibility to produce a denition of life range
widely. At the extremes (and without necessarily being wrong) some authors may
claim that a technically accurate denition of life is not needed or impossible.
Assuming that a denition for life is needed and possible, it has to obey two basic
requirements: to be coherent relative to what we already know about life, and the
philosophy used to produce the denition has to be clear of systemic errors. The
method proposed by Edward Trifonov to dene life (1) is a minimalist vocabulary-
based screening, combined with a personal interpretation of the meaning of the
ndings. Is this method consistent with the requirements listed above, and what
novelties it introduces in our understanding of life?
The method proposed is seemingly simple. Take a large collection of denitions
of life and calculate the frequency of different words (Table I in the original
article). Identify the most common words and the words with similar meaning
(Table II in the original article) and combine them in a rst-hand denition. Then,
shorten by eliminating terms and concepts that imply each other, in a way that
allows essence and causes rather than trivia and consequences to be retained in a
nal denition.
Following this logic, the manuscript (1) should have ended with the analogy with
Principal Component Analysis (p. 262). The author however nds more thrust
to continue the manuscript past this point, by discussing issues such as thermo-
stability, GC rich sequences, information complementarity and RNA-related
almost precise replication. If the aim of this study (1) was to summarize why
RNA-related molecules are important for biological life on Earth, then I nd
it insightful. If one however expected for this study to be a non-earth-centric
attempt to dene life, the focusing of the closing arguments on physical-chemical
and informational properties of a particular class of molecules is distracting and
unfullling.
It is also necessary to analyze the validity of the key premise of this paper. It is
obvious that the scientic community cannot bring itself together to produce and
support a singular denition for life. The motives and the diversity of various
opinions are not discussed here, only their consequences on a vocabulary-based
strategy to dene life. The essence of a vocabulary method is that words and ideas
that are the most common must also be the most important. This is true to a point.
It does apply very well to elds where basic research has more or less ended, yet
it makes it difcult for pioneers and novel theories to gain recognition, irrespec-
tive of how right they are. For example, if we promote a scientic model based
Radu Popa
E-mail: rpopa@pdx.edu
Radu Popa
Portland State University,
P.O. Box 751, Portland,
OR, 97207, USA
608 Popa
on popularity, then Alfred Wegener was correctly ignored
in 1912, when he promoted the concept of continental drift.
One example from the eld of the origin of life is Kunins
contribution, which was used to explain the initiation of a liv-
ing system as a symbiosis between two molecular networks
(e.g. a protein-made RNA polymerase cooperating with an
RNA-made protein polymerase) (2). This great contribution
to understanding the essence of life would be considered
unworthy of mentioning by a vocabulary-based method,
simply because it is seldom cited in origin of life models.
If we leave it to a computer-selected one-word-at-a-time
vocabulary to dene the essence of life then some seldom,
yet worthy, characteristics of life would be dropped as little
relevant. Take for example complex concepts such as adap-
tive evolution, cryptic information and energy dissipative
systems. The combination adaptive evolution is richer in
meaning than the term evolution. Evolution and variability
exist in both alive and non-alive systems, yet living systems
have an edge for survival by being built for adaptive evolu-
tion. Also, in all life forms that we recognize on earth today
the genetic information is encoded. This is a very important
attribute of life because it allows living entities to accumulate
a collection of virtual realities (dissimilar states) that are all
possible but do not interfere with each other, because when
one is expressed all others are hidden. Obviously, the simple
term information is too poor in meaning to describe the com-
plexity of what life does. Lastly, if we discard the connection
between the energy dissipative properties of living systems
and their capacity for self-control we loose the very reason for
the origin of life (3, 4).
Can life be reduced to a collection of dimensionless qualities,
or it has some properties that require reaching specic size
before a system can become alive? The obvious example is
the complexity-level analysis made by Stuard Kauffman (5),
which a vocabulary analysis will simply ignore. The lesson
learned from Dr. Trifonovs approach is that we can circum-
vent such limitations by analyzing major consequences of
being alive rather than analytically dissect and list all lifes
properties and achievements.
At the syntactic level a denition cannot be constructed as
a popular saying that leaves grammatical parts in limbo. In
order to be useful, the construction of a denition has to obey a
specic set of minimal rules. The expression, Life is self-
reproduction with variations albeit inspirational, does not
inform whether life is a physical system or the property of a
physical system. This denition does not clarify whether these
features are restricted to life or if they may also occur in other
systems that are not alive. Lastly, is this denition sufcient to
explain life or is it just one important aspect of it? The analysis
from (1) correctly replaces this truncated denition with a gram-
matically correct one developed by Oparin (6): Any system
capable of replication and mutation is alive. This is not however
sufcient reason to accept Oparins denition of life as complete,
because it still lacks many important properties of life.
Last but not least, can life exist that is not RNA-based? If the
answer is YES, then no need exists to pound on the RNA-world
drum in order to explain what life is. If NOT, then the author
(1) has to state that no alien life can exist unless it is based on
RNA-like molecules, which everybody will probably doubt. To
summarize, one recognizes in a vocabulary method the need to
resolve present ambiguities about dening life though, in my
opinion, not the best avenue for reaching this goal. This aside,
the reader interested in the subject of dening life and explain-
ing its early evolution will nd sufcient substance in (1) to
make this article worth reading and instructive. Ultimately,
We may never agree on a denition of life, which will remain
forever subject to a personal perspective. The measure of ones
scientic maturity may actually be his/her latest denition of
life and the acceptance that it cannot be ultimate (7).
References
V. Kunin. 2. Orig Live Evol Biosph 30, 459-466 (2000).
P. Bak. How nature works. Copernicus, New York (1996). 3.
E. Chaisson. 4. Int J Astrobiol 2, 91-101 (2002).
S. A. Kauffman. The origins of order, Oxford University Press, 5.
New York (1993).
A. I. Oparin. Life: its nature, origin and development, Academic 6.
Press, New York (1961).
R. Popa. 7. Orig Live Evol Biosph 40, 183-190 (2010).
609
Comment
Self-Generated and Reproducible Dynamics in
Gene Years Represent Life
In a recent article (1), Trifonov has developed an approach, conceptually inspired
by principal component analysis (PCA), for arriving at a consensus denition of
life as self-reproduction with variations. In appreciation of the sound analyti-
cal effort applied rigorously on a comprehensive body of literature, I will refer to
both the approach and the denition as Trifonovian. The Trifonovian approach
has to be commended in its effort to evolve a minimalistic, and at the same time an
all-inclusive, denition of life. In fact, from the literature on molecular components
of living systems, the Trifonovian denition of life is clearly a direct reection of
the ideas of consensus sequences at the level of DNA/RNA and (in specic cases)
even proteins, and homology modeling (including minimal functional motifs) in
protein structures. Thus, while appreciating the Trifonovian approach, it is also
important to carefully consider the severe limitations of consensus/similarity
approaches (applied for the molecular components) that have pushed the limits of
experimental (both computational and wet-laboratory) biology into increasingly
complex/sophisticated formalisms that have unfortunately not provided univer-
sal insights till date. In fact, some universal insights have been achieved only by
comprehensive (computational and/or wet-laboratory) rather than consensus based
approaches (2-5).
Limitations of the Trifonovian Denition of Life
A denition is expected to explain (and not just summarize) the meaning of
a term. Scientically, a denition has to be able allow extraction of parameters
that will enable a mechanistic understanding of the term in view of the scientic
method of Observation Hypothesis Experiment Mechanism. Thus,
the obvious question arises why is a denition of life required? My answer
to this question involves the following aspects A denition should allow
(a) extraction of parameters, open to theoretical analyses and/or experimentation
(computational/wet-laboratory), useful in providing mechanistic insights into
life eventually leading to rules that can allow classication of a system as
living or non-living, and, (b) a clear establishment of both necessary and suf-
cient requirements to be able to not just provide an understanding on the origin(s)
of life but also lead to methodologies towards synthesis of life de novo. In this
regard, the Trifonovian denition fails to address the above aspects either par-
tially or in totality. For example, variation in the denition of life is subject to
variation in the environment. If the environment was a static/stagnant variable,
then variation in the denition of life would not be required (since variation
in life is not observed in a static/stagnant environment). Further, the Trifonovian
denition fails to address the molecular dilemma in realizing self reproduction
within the constraints of conservation of mass and energy (i.e., exchanges with
Aditya Mittal
Phone: 191-11-26591052
E-mail: amittal@bioschool.iitd.ac.in
Aditya Mittal
Kusuma School of Biological Sciences,
Indian Institute of Technology Delhi,
New Delhi 110016, India
610 Mittal
the environment must be built-in). On a trivial (and some-
what philosophical) level, the Trifonovian denition fails to
classify sterile living systems (e.g., male mules) as a part
of Life.
Molecular Outlook for Developing a Denition of Life
Extending the spirit of appreciating a requirement for the de-
nition of life, let us carefully consider our understanding of
a living system from the molecular perspective in terms of a
unit of life, i.e. a cell. Figure 1A shows the basic molecular
machinery of a unit of life. The molecular entities involved
in giving a cell its identity as a living system in terms of
the central dogma (6) are shown, though a few recently dis-
covered exceptions to the central dogma have be reported
recently (7-9). A living cell has evolved through presence
of a single or several proteins resulting in phenotypic traits
that are retained or lost in response to environmental changes.
Interaction between the components of the proteome and the
environment results in governing the dynamics and balance of
the proteome to keep the cell as a unit of life in a given envi-
ronment. Coding to construct this proteome is well guarded
in two layers of code, neither of which readily interacts with
the environment. Variations in this unit of life, in response
to environmental changes, can result from either the feedback
from the proteome to the genome, or, interaction between the
(A)
Code DNA (Genome)
Coded Message RNA
Phenotype Protein (Proteome)
Environment
Environment
Cell Unit of Life
Environment
Code/Coded Message RNA (Genome)
Phenotype Protein (Proteome)
Environment
Cell Environment 1
Cell Environment 1
Virus Non-Living by itself
(B)
Figure 1: Molecular understanding of life and
evolution. (A) A cell, considered (and dened) as a
unit of life, is shown as a grey box. The molecular
entities involved in giving a cell its identity as a
living system in terms of the central dogma are
shown. The environment is shown as a blue box.
Components of the proteome interact with the envi-
ronment (shown by bi-directional black arrow).
Coding to construct this proteome is well guarded in
two layers of code, neither of which readily interacts
with the environment. Variations in this unit of
life, in response to environmental changes, can result
from either the feedback from the proteome to the
code i.e., the Genome (shown by the uni-directional
dashed black arrow), or, the more direct interaction
between the code and the environment (shown by
the bi-directional red dashed arrow). (B) An exam-
ple of RNA virus (white box) is shown, where the
code/coded message interact with two levels of envi-
ronments (cell grey box: Environment 1, and the
Environment of the cell/free-virus itself), in addition
to the interactions of the proteome.
Self-Generated and Reproducible Dynamics in Gene Years Represent Life 611
code and the environment. The former is responsible for accu-
mulating variations over time leading to the slow process of
evolution. For example, a protein not involved in interaction
with the environment is gradually not present in a form to pro-
vide any feedback and thus is not further synthesized from the
code. The resulting loss of this protein inside the cell gives rise
to different phenotypic traits (variation). However, if the latter
was possible, substantial variations would be observed in liv-
ing systems at very short time scales. Even more drastically,
in many cases life would not self-reproduce, since substantial
variations would occur even with minor changes in the envi-
ronment. Simply put, if the code was directly interacting with
the environment, minor changes in the environment would
yield sufcient changes in the code that could be amplied to
form new life forms, rather than self-reproducing life forms.
Every reproduction cycle would give rise to a new life form.
Figure 1B shows an example of RNA virus, where the code/
coded message interact with two levels of environments, to
support the above. For the virus, cell is the rst level of environ-
ment that it has to interact with, referred to as Environment 1.
However, since the virus has direct interaction of the code
with its environment in addition to the proteome interacting
with the environment, changes in the living form of virus is
observed at very short time scales. This is true for all known
RNA viruses (without exception). Thus, it is essential to
appreciate that it is the phenotype that interacts with the envi-
ronment, and only those living systems have survived (or will
survive) in terms of self-reproduction in which the genotype
(i.e., the code for creating phenotype) is not (or minimally)
capable of interacting with the environment.
Self-Generated and Reproducible Dynamics
in Gene Years Represent Life
Based on the above discussions, and inspired by the Trifonovian
approach, it is desirable to utilize the comprehensive body of
literature for arriving at a denition of life. However, it may
be more useful to extract some universal concepts/principles
discussed in Trifonov (1). It is clear that two key features must
be built into a denition of life: Kinetics and Self-assembly.
Note that I have specied the two features in form of paramet-
ric variables that can be scientically explored. Denition of
life must specify its ability to self-generate (rather than self-
reproduce with variations in response to the environment). The
term self-generation accounts for a variety of self-assembly
processes within living systems. The terms reproducible
dynamics account for organized kinetic processes required for
maintenance and self-generation properties of living systems.
They also signify the importance of reproducing the dynamics,
rather than the individual components behind the dynamics.
In fact, at a molecular level, several features observed in and/or
for living systems show dynamic behavior that, while stochas-
tic in the actual initiation, follow clear and systematic kinetic
modes from starting of an event to their completion regardless
of the system and the technique (10-12). Finally, I would like
to propose that analogous to the astronomical unit of light
years (for length-scales in the universe) it will be useful to
develop an evolutionary unit of gene years that can allow an
understanding of time-scales for evolution of life and length-
scales for genomes in the proposed denition of life.
References
G. N. Ramachandran, C. Ramakrishnan, and V. Sasisekharan. 2. J Mol
Biol 7, 95-99 (1963).
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1166 (2007).
613
Comment
A Minimal or Concise Set of Denition
of Life is Not Useful
Trifonovs interesting analysis (1) appeared to have highlighted a minimal set
of popular vocabulary in the literature that constitutes a concise and inclusive
denition for life. Dened as such, Life is self-reproduction with variations.
The linguistic and philosophical worth of the paper notwithstanding, its scientic
value is, however, questionable. This minimized denition of life misses out on
an important property, namely lifes capacity for integrating chemical processes
that sustains the living entitys low entropy (i.e., metabolism). Importantly, the
denition has no bearings on the origin of life (2-6), and ignored the myriad of
possible transitions from a collection of abiotic chemical reactions to a form that
could be subjected to Darwinian selection (7, 8). Though undoubtedly concise
enough, it is far from being inclusive.
A quick glance at the denition of Life is self-reproduction with variations
brings to mind two potential deviations, both of which might nonetheless be rec-
ognized as life. Firstly, obligate parasites (the simplest of which being viruses) are
in the strictest sense incapable of self -reproduction. Intriguingly, the number
of viruses on the planet exceeds that of cells almost by an order of magnitude (9),
and the pivotal role of viruses in the evolution of the biosphere is now increas-
ingly recognized (10). Secondly, terminally differentiated cells, of which neurons
would be prime examples, are incapable of replication. Neurons are nonetheless
metabolically active, long living entities that last the life span of the animal. For
that matter, senescing eukaryotic cells, which had exited the cell cycle and could
no longer undergo cell division, could remain metabolically active for a good
length of time. On the other hand, at least from a biocentric perspective, a self-
replicating computer virus or a Von Neumann probe (11) programmed to allow
variations or mutations in their replications, which are not usually considered
as leading candidates for life forms, could have their candidature legitimized by
Trifonovs minimized denition. Although the author deemed the generality of
the minimized denition as being an unforeseen and favorable property, it could
just as easily be viewed as an undesirable oversimplication.
A more disappointing feature of the minimized denition is its failure to con-
nect with the problem of the origin, or emergence of life. Although probably not
by design, results of the authors linguistic analysis appear to bias towards the
gene-rst or replicator-rst school of thought, and have rather marginalized
the metabolism-rst theories. Various forms of the gene/replicator-rst theo-
ries, including the RNA world (12), depict the emergence of a self-replicating
molecule and a self-replicating process that could be subjected to Darwinian
selection. The metabolism rst models, on the other hand, emphasize on the
Bor Luen Tang
Phone: 65 516-1040
Fax: 65 6779-1453
E-mail: bchtbl@nus.edu.sg
Bor Luen Tang
Department of Biochemistry,
Yong Loo Lin School of Medicine,
National University of Singapore, MD7,
8 Medical Drive Singapore 117597,
Republic of Singapore
614 Tang
importance of self-sustaining prebiotic chemical reac-
tions that culminates into the earliest form of metabolism.
Examples of these include the classical Wchtershusers
Iron-sulfur world (13), and later proposals such as the
thermodynamically sustainable autocatalytic cycles as
expounded by Shapiro (14). Both schools of thought have
merits in certain regards, while harboring their own short-
comings. These have been extensively discussed elsewhere
(8, 15, 16) and shall not be elaborated. Sufce to note here
that the minimized denition fails to capture the large vari-
ety and possibility in terms of prebiotic pro-metabolic reac-
tions that are chemically conceivable, and their transitions
into Darwinianly selectable life.
A further consideration of this disconnection between this
minimized denition with lifes origins concerns the sites
involved. In a sense, the exact physical and chemical prop-
erties of life could be situation and locale dependent. On this
planet itself, life could have emerged more than once (18),
and at different geological sites (7, 8). The minimized de-
nition fails to illustrate the myriad of possibilities of lifes
emergence in space and time such as those from the hot
hydrothermal vents of early Earth 4 billion years ago to the
warming organic lakes of Titan another 4 billion years from
now (17).
Along a similar line of thought, I could not share the authors
optimism that day is not far away when life could be cre-
ated in a test tube. Never mind that Spiegelmans monster (19)
represents a state of degenerated complexity that is unlikely
to eventually acquire a degree of respectable, self-sustaining
metabolism that is capable of adaptation and evolution, all
other attempts to model life to date have involved starting
materials that are far too complex that would have been
available prebiotically. There is no evidence that a Miller-
Urey type experiment ever yielding polymers of a signicant
length, not with the opportunity and rate of a chain terminating
reaction far exceeding that of spontaneous polymerization. In
Kompanichenkos terms, we have no idea of the condition(s)
that would generate oscillating prebiotic microsystem at a
balanced bifurcate state, let alone those that would facilitate
inversion of the balance free energy/entropy contribution
and the rise of the key biological properties (20).
In view of the above, it seems reasonably clear that a popular
or consensus minimalistic denition of life may not be very
useful, and could in fact be misleading. This notion does
not undermine the two principal features of the denition,
namely self-reproduction and variations (which implies
a propensity to undergo Darwinian selection), but rather
suggests that our understanding of life in the universe might
actually benet from a broad denition with a wide range
of vocabularies. A more wordy denition may appear more
cumbersome, but its worth the trouble. In the context of
Trifonovs paper, denition (1) is more useful than denition
(2). The latter, like Spiegelmans monster, is less exciting.
References
J. W. Szostak. 2. J Biomol Struct Dyn 28, 1059-1059 (2011).
U. J. Meierhenrich, J.-J. Filippi. C. Meinert, J. H. Bredehft, 3.
J.-i. Takahashi, L. Nahon, N. C. Jones, and S. V. Hoffmann. J Biomol
Struct Dyn 28, 1060-1061 (2011).
G. Costanzo, S. Pino, F. Ciciriello, and E. Di Mauro. 4. J Biomol Struct
Dyn 28, 1061-1061 (2011).
J. P. Ferris, P. C. Joshi, M. F. Aldersley, and J. W. Delano. 5. J Biomol
Struct Dyn 28, 1062-1062 (2011).
A. E. Engelhart, R. Buckley, E. D. Horowitz, and N. V. Hud. 6. J Biomol
Struct Dyn 28, 1063-1063 (2011).
B. L. Tang. 7. J Br Interplanet Soc 58, 218-222 (2005).
B. L. Tang. 8. Prog Nat Sci 17, 500-510 (2007).
A. Abroi and J. Gough. 9. BioEssays 33, 626-635 (2011).
L. P. Villarreal and G Witzany. 10. J Theor Biol 262, 698-710 (2010).
R. A. Freitas, Jr. 11. J Br Interplanet Soc 33, 251-264 (1980).
W. Gibert. 12. Nature 319, 618 (1986).
G. Wchtershuser. 13. Prog Biophys Mol Biol 58, 85-201 (1992).
R. Shapiro. 14. Q Rev Biol 81, 105-125 (2006).
R. Shapiro. 15. IUBMB Life 49, 173-176 (2000).
J. Perat. 16. Int Microbiol 8, 23-31 (2005).
R. D. Lorentz, J. I. Lunine, and C. P. McKay. 17. Geophys Res Lett 24,
2905-2908 (1997).
P. C. Davies and C. H. Lineweaver. 18. Astrobiology 5, 164-163 (2005).
D. R. Mills, F. R. Kramer, C. Dobkin, T. Nishihara, and S. Spiegelman. 19.
Proc Natl Acad Sci USA 72, 4252-4256 (1975).
V. N. Kompanichenko. 4 20. Int J Astrobiol 7, 27-46 (2008).
615
Comment
On the Misgivings of Anthropomorphic Consensus
Polling in Dening the Complexity of Life
In a recent paper (1) Edward N. Trifonov has turned his statistical expertise on
one of the most enigmatic questions still vexing our scientic conceptions of the
universe: What is life? If applied ingeniously, statistical methods are marvelous
tools indeed, but yet, they hardly breed miracles on their own. To be sure, profes-
sor Trifonov has done wonderful work before, scrutinizing the system of coded
protein synthesis for innate secrets by sophisticated statistical analyses (2-4).
To start with, many others have put forth various denitions of the living state as
such in contrast to non-living matter, which pervades most of the observable
universe. By tabulating 123 versions of such learned statements (partly overlap-
ping, that is, but slightly or distinctly different from one another), and to simplify
matters, Trifonov (1) has now applied his statistical tools on the wording of these
denitions. Would the grouping of major terms by related meaning, as followed
by word counts of occurrence in the major groups, yield any superior, canonical
relationship? Nota bene, not just a meaningful concept at a superior level, but
a universally applicable, novel and minimalistic denition of life as such, to the
inclusion of any forms of life imagination may offer? Although he does not
meticulously discern what properties should be required of such a universal de-
nition, Trifonov proposes to have found exactly that, as merely based on just two
terms: Life is self-reproduction with variations. In fact, this punchline was put
forth earlier (4), as an aphoristic rephrasing of Darwins principle.
The author must have found it reassuring that an earlier hunch of his could be
extracted as a consensus from a much larger sample from the expert literature,
although only ~15% (18 of 123) happened to contain a pair of terms related to his
condensate. Moreover, by explicitly referring to Oparin [as cited in (5)] Any
system capable of replication and mutation is alive Trifonov moves close to
implying that his minimalistic denition may not only be necessary but even suf-
cient for sorting out the living state from non-living matter. On the other hand,
he likens his statistical vocabulary approach to a Principal Component Analysis
(aimed to reduce a complex data set to an array of subsets that vary independently
of one another) with the extraction of a single principal component (the major
one, covering most of the data), which might serve as the main characteristic of
the living state so far, so good.
Yet, as the author himself is quite aware, Even most primitive forms of observ-
able life are still too complex, to claim that they can be reduced to the above
simple formula (1). Hence, it is rather premature to adopt his simple formula
as the dening principle of any forms of life imagination may offer. As to
my personal imagination, for that matter, I should not hesitate to subsume frost
Richard Egel
E-mail: regel@bio.ku.dk
Richard Egel
Department of Biology,
University of Copenhagen Biocenter,
Copenhagen, Denmark
616 Egel
tracery on a window pane or frostwork-type mineralizations
in cave deposits under this generally dened set of natural phe-
nomena. They actually replicate certain preexisting patterns,
and do so with many variations, but calling them life-like
for more than a rather supercial resemblance should be
besides the point, I guess.
There are good reasons to suggest, therefore, that Trifonov
should not stop at the very rst principal component of his
statistical vocabulary ltering approach. Additional compo-
nents, likewise both principal and indispensable for zoom-
ing in on the essence of life, should not lightly be dismissed
beforehand. Alternatively, the intended meaning of the main
part in his favorite component self-replication should be
specied so distinctly and concisely that no form of non-
living matter imagination may offer might ever qualify for
having that capacity. If, and only if this precondition has been
met can self-replication be considered equivalent conceptu-
ally and empirically to life as such. And what a big if that
is, since now the burden of dening the complexity of life in
simple terms has shifted to dening self-replication and its
preconditions at the same level of life-like complexity.
In this brief discourse I have deliberately focused on the main
part of the composite formula, Life is self-reproduction
with variations, since the secondary part does not add a new
dimensionality to the problem at all. To be precise on this,
self-reproduction without variation would be entirely cti-
tious, in that it can never be realized as a natural process. In
fact, in the course of biological evolution of earthly life as we
know it the multiple sources of stochastic variation in repro-
ductive processes have progressively been narrowed down to
acceptable and affordable levels, but eliminating each of such
sources once and for all is beyond the bounds of possibility.
Why should the essence of life as such be dened in idealistic
or anthropomorphic terms in the rst place? Who would actu-
ally benet from such a canonical denition if it ever existed?
While most biologists in general do not care, it is foremost some
non-biologists trying to comprehend the enigmatic origins of life
from non-living matter who are convinced that their goal cannot
be reached without having dened life as such beforehand. Yet,
not all such scholars share this conviction, and personally I very
much tend toward the sceptical side on this dividing issue (6).
In defence of this sceptical stance, I consider it more relevant for
a comprehension of biological complexity to familiarize with
the principles of fuzzy sets and fuzzy logics (7). This should not
be denounced as fuzzy thinking in a pejorative sense. Rather, it is
to appreciate the appropriateness of variance-loaded terms and
categories for about every aspect of the natural world, including
life with all its intrinsic complexity and evolutionary history.
At the initial stages, lifes emergence had to cope with much
higher degrees of variance than what is presently observed in
the current biosphere. Hence, putting coordinate restraints on
stochastic variance in ever so many independent categories by
natural selective processes should be at the forefront of how to
understand the living state.
To illustrate the anthropomorphic character of certain
unreected denitions, I should like to draw on a compari-
son of German and English conventions concerning food
intake. While it should sound sensible enough in German to
dene the human species as das essende Wesen, the
direct translation into English would make no sense: the
eating creature would cover most animals alike. British
pragmatism, at least on this issue, allows animals at large to
eat their food as well, whereas essen in German is a decid-
edly human privilege, in contrast to fressen, as used for
the equivalent activity in animals. Such a pseudo-denition,
however, would be rather trivial indeed, a human being is
a human being, Period!.
In summary, the statistical vocabulary approach of Tifonov (1)
to extract a simple dening formula for the intrinsic complex-
ity of life amounts to an enchanting exercise on the border
between basic science and aphoristic poetry. I was somewhat
reminded of my rst visit to the United States in the mid six-
ties, when a frenzy orished among high school kids to come
up with the most fanciful variation on Happiness is ....
References
E. N. Trifonov. 2. Gene 261, 139-151 (2000).
E. N. Trifonov. 3. Phys Life Rev 5, 121-132 (2008).
E. N. Trifonov. 4. Res Microbiol 160, 481-486 (2009).
R. Popa. 5. In Between Necessity and Probability: Searching for the
Denition and Origin of Life. Series: Adv Astrobiol Biogeophys,
Springer, NY, pp. 197-205 (2004).
R. Egel. Integrative perspectives: In quest of a coherent framework 6.
for origins of life on earth. In Origins of Life: The Primal Self-
Organization. Egel, R., Lankenau, D.-H., and Mulkidjanian, A. Y.
(Eds.), Springer-Verlag, Heidelberg, GE, pp. 289-360 (2011).
G. Bruylants, K. Bartik, and J. Reisse. 7. C R Chimie 14, 388-391 (2011).
617
Comment
The Complexity of Life: Can Life
be Simply Dened?
In the interesting article by Trifonov (1), the denitions of Life were analyzed
from a variety of sources and 10 groups of terms were compiled. Based on these
terms, the author attempts to provide a succinct denition of what Life is; that
is, Life is self-reproduction with variations. While the terms underpinning the
denition clearly provide a reasonable characterization of Life, there appears to
be a lack of certain key elements of what Life embodies.
One of the main issues with the denition as based on the vocabulary used is that
there is no mention that Life, as it had evolved (2-6) on earth, came about without
a purpose. One of the denitions the author had quoted was from Kompanichenko
who stated that the category of terms that encapsulates the denitions of Life
is one that includes, among other characteristics, the display of self-perfecting
logic. First of all, there is a slight problem with the term self-perfecting, as it
tends to give the impression that there is a teleological attempt by Life to drive
towards a particular aim such as survival or an increase in complexity. Secondly,
words under the category of Ability more often than not promote the perception
that living things are consciously able to respond physiologically to external envi-
ronment and to evolve accordingly, rather than there being a selective pressure
exerted by the external environment, thereby sieving out organisms not suited for
survival in that particular circumstance.
As argued by Richard Dawkins (7), Life evolved without an aim or a purpose.
As such no pre-determined conditions existed that favoured a particular life form
over another or any life forms for that matter. Conversely, organisms are not capa-
ble of evolving specically to adapt to various conditions on Earth. The process of
evolution, as expressed by Franois Jacob (8), is one of tinkering, during which
the selective process works on what already exists, either transforming a system
to give it a new function or combining several systems to produce a more complex
one. That vestigial organs or lack of a perfect design in organisms (9) can be
found today supports this notion. While the author (1) was relying on terms previ-
ously used to derive a concise denition of Life based on the frequencies of their
usage, I would suggest that there could be a description to reect Life as an entity
or property that is amenable to (natural) selection without a purpose (direction).
In addition, words such as organization and information under the groups system
and complexity do not completely embody the idea of emergent properties that
relate to developmental biology at the individual organism during embryogenesis,
as well as for the entire collection of living organisms. As put forth by Oyama (10),
there appears, at least during the development of a multicellular organism, to
be more than the information encoded by genes. Indeed, the interaction among
cells is critical during development to ensure the proper unfolding of the resulting
Foong May Yeong
E-mail: foong_may_yeong@nuhs.edu.sg
Foong May Yeong
Department of Biochemistry,
Yong Loo Lin School of Medicine,
MD7, 8 Medical Drive,
Singapore 117597
618 Yeong
organism. Such an important essence of Life, where invari-
ant properties such as information encoded in the genes and
how cells interact with its environment determine how multi-
cellular organisms develop, might need to be included in the
denition of Life.
Likewise, the terms under the section on evolution appear
to fall short of representing the full complexity of how organ-
isms can evolve as part of being a living thing. Currently, there
is a trend towards examining the evolvability of organisms
as an extension of the ideas behind the Modern Synthesis
of evolutionary biology (11). This is based on the authors
count of 364 papers in which this word had been used (11).
Simplistically, evolvability can be loosely referred to as
the propensity of a genotype to generate variability and as
such, determine the success of a species during natural selec-
tion. While the notion of evolvability has not been formally
dened and empirically validated, based on the authors argu-
ment, I suggest that the concept might eventually be a more
useful one to explain mechanistically how different species of
organisms could have arisen. This term does not seem to be
encapsulated in the short denition of Life that is provided
(1) and it is not clear if it could be in the future. Furthermore,
the denition should encompass the notion that while the var-
ious properties of Life as complied (1) are carried within
each living organism, it is the collective existence all living
things as a result of organisms interacting with the environ-
ment that we are able to witness the phenomenon of Life.
The denition of Life is important as it is needed for philo-
sophical and practical reasons (12). Given the complex nature
of Life, it might require a more elaborate denition (13) to
cater to specic applications (14) than simply being distilled
from the vocabulary of previous denitions of Life to be of
practical use.
References
W. L. Duax, R. Huether, D. Dziak, and C. McEachon. 2. J Biomol Struct
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R. Dawkins. The Blind Watchmaker: Why the Evidence of Evolution 7.
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S. Oyama. The Ontogeny of Information, Duke University Press 10.
(2000).
M. Pigliucci 11. . Nat Rev Genet 9, 75-82 (2008).
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R. Popa. 13. Orig Life Evol Bioshp 40, 183-190 (2010).
J. D. Oliver and R. S. Perry. 14. Orig Life Evol Bioshp 36, 515-521 (2006).
619
Comment
The Role of Logic and Insight in the Search
for a Denition of Life
In a recent paper Trifonov (1) has carried out a statistical analysis of the fre-
quency of the vocabulary used in 123 existing denitions. The goal is to identify
the most important words and to use these for phrasing a commonly acceptable
denition of life. Trifonov arrives at the conclusion that (self-)reproduction and
evolution form the minimal set for a concise and inclusive denition: Life is self-
reproduction with variations. Also a more lengthy denition is presented: Life
is metabolizing material informational system with ability to self-reproduction
with changes (evolution), which requires energy and suitable environment.
Trifonovs work is part of the important and long standing quest in science and
philosophy for a commonly acceptable denition of life (2-7). While reading
Trifonovs publication a few questions came to my mind.
The rst question is why the author suggests using a vocabulary method instead
of insight when dening life? I am worried that although the use of vocabularies
may represent a proper tool for identifying keywords and the like, the methodol-
ogy seems fundamentally inappropriate for suggesting denitions. Would any
denition process not require the logical integration of scientic insights and
thorough testing by confronting them with difcult cases? It is not clear to me
how vocabulary studies meet such criteria, because the ranking of words accord-
ing to frequencies seems blind to the underlying logical relationships.
My second question involves some methodological aspects of using vocabulary
analyses for creating denitions.
1. Can lists of denitions reect recent developments? Innovative insights
will in general require several years to become generally referenced in
the literature. In addition, recent studies will generally relate to advanced
scientic insights and may not use conventional wording. Would this
effect potentially bias lists of denitions towards past and potentially aged
insights?
2. Has the list of denitions been checked for dependence of information? It
is general practice to use old masters as a basis when improving deni-
tions. Such practices are likely to cause biases towards certain words in
denitions inspired by the most inuential examples.
3. How to extract meaningful results if vocabulary studies take words lit-
erally? Denitions frequently originate from different worldviews. As
a consequence, the meaning of the words may differ between deni-
tions. For example, some people use life for indicating all ecosystems
Gerard A. J. M. Jagers op Akkerhuis
E-mail: gerard.jagers@wur.nl
www.hypercycle.nl
Gerard A. J. M. Jagers
op Akkerhuis
Center for Ecosystem Studies, Alterra,
Wageningen University,
6700 AA Wageningen, The Netherlands
620 Jagers op Akkerhuis
and organisms on earth (life on earth), while others
think of the length of the period between birth and
death (he had a long life) or of daily existence (my
life as a teenager). How has the study accounted for
the summation of words with different meanings?
4. Would the vocabulary method recognize the confusion
that presently exists with respect to the word life?
Many well-known denitions of life actually refer to
concepts related to living, for example metabolism,
activity, reproduction, etc. As has been suggested by
the author of this comment, it may be protable to sci-
ence when life would be used to describe organisation,
while living is used in relation to the dynamics of those
organisations representing life. This distinction was
already recognized by the famous Socit de Biologie
in Paris (8). Examining frozen or dried bacteria, the
Society concluded that the potential to revive an anabi-
otic stage is an inherent aspect of the organisation of
the material of which the object consists and that it is
equally persistent as the molecular state of the matter
forming the system. The society concluded: La vie,
cest lorganisation en action. In other words, living
refers to the dynamics of organization(s) that represent
life. How would vocabulary studies assist in identify-
ing which organisation(s) represent life?
5. How do vocabulary studies distinguish between
appropriate and inappropriate denitions? With-
out such distinction, the most popular concepts will
always be partly associated with inappropriate de-
nitions. How can statistics on vocabulary circumvent
the problem of deciding about the correctness of a
given denition?
My third question involves the testing of denitions based
on vocabulary analysis. Any commonly acceptable denition
must be able to deal with difcult cases. What happens if
we undertake this exercise using the above denitions? How
about a sterilized cat? If I understand the above denitions
well, this cat would not be a living being because it cannot
self-reproduce. Even a normal fertile cat is a problem. It
cannot self-reproduce, because it needs the males sperm.
And a frozen bacterium? While being frozen, it is neither
metabolically active nor can it reproduce. Not life accord-
ing to the above denitions. But a frozen bacterium still pos-
sesses the structure of life, which can be demonstrated when
it resumes living activity after being thawed. How to value
the above denitions in the light of these results?
In relation to the above questions, I would like to invite the
author to take an interest in a recently developed frame-
work that uses the evolution of complexity as a basis for
dening life. In order to analyse the organisation in nature
in a stringent way, the author of this comment developed
the Operator Hierarchy (9, 10). This hierarchy represents a
ladder ranking all types of physical particles and types of
organisms, generically indicated as operators, according to
discrete transitions in the complexity of their organisation.
As has been advocated in a previous publication about the
denition of life (11), this ladder offers a fundamental basis
for dening life as a common property of all types of entities
on the ladder (the operators) that are equally or more com-
plex than the cellular operator (bacteria s.l.). From this point
of view, talking about life implies a focus on the presence
of the level-dening organisation in selected operators. As
long as the level-dening organisation is present, the entity
represents life. And when an entity that represents life is
dynamically active, it is living. Consequently, death implies
the loss of the level-dening organisation. Biologists gener-
ally consider all the operators with a minimum complexity
of the (bacterial/prokaryotic) cell as organisms. The com-
plexity ladder of the operator hierarchy thus offers an under-
lying logic connecting the concepts of life and the organism.
The ladder therewith solves an old circularity problem that
occurs when life is referred to as a property of organisms,
while organisms are dened as living beings. As has been
discussed in (11), the operator based denition of life deals
without problems with a broad range of difcult cases.
Assuming that dening life requires the logical integration of
scientic insights and thorough testing of the results by con-
fronting them with difcult cases I was inspired to a range
of questions about specic aspects of the use of vocabulary
study for dening life. I nd it worrisome that the method
seems not to invoke insight and that the resulting denitions
seem to have problems with simple test cases. I hope the
author can take away my worries in his response.
References
R. Popa. Between necessity and probability. Searching for the denition 2.
and the origin of life. Advances in Astrobiology and Biogeophysics.
Springer (2003).
D. E. Koshland, Jr. 3. Science 295, 2215-2216 (2002).
C. Emmeche. 4. Ultimate Reality and Meaning 20, 244-264 (1997).
M. A. Bedau. What is life. In: Sarkar, S. and Plutynski, A. (Eds.), 5.
A companion to the philosophy of biology, pp. 455-603 (2007).
C. E. Cleland and C. F. Chyba. Does life have a denition? In: 6.
Planets and Life: The Emerging Science of Astrobiology, Woodruff,
T., Sullivan, I. I. I., and Baross, J. A. (Eds.), Cambridge University
Press (2007).
J. M. Maynard Smith and E. Szathmry. The origins of life. Oxford 7.
University Press, Oxford (1999).
P. Broca. 8. Mm Soc Biol 3me Srie II, 1-139 (1860).
G. A. J. M. Jagers op Akkerhuis and N. M. van Straalen. 9. World
Futures, the Journal of General Evolution 53, 329-345 (1999).
G. A. J. M. Jagers op Akkerhuis. The operator hierarchy, a chain of 10.
closures linking matter, life and articial intelligence. PhD thesis,
Raboud University, The Netherlands (2010).
G. A. J. M. Jagers op Akkerhuis. 11. Found Sci 15, 245-262 (2010).
621
Comment
Life 5 Self-Reproduction with Variations?
Trifonovs paper (1) is a delightfully clever, objective and quantitative approach
to dening life. Doing a linguistic analysis of 123 published denitions of life,
Trifonov tabulates the words used in these denitions, to seek a consensus deni-
tion of life. This approach synthesizes some of the thinking and work of hundreds
of scientists, and non-scientists as well.
Popa (2) contributes 90 of the denitions used by Trifonov. Popas list of 90
denitions of life is an unusual one. Historically, it is impressive, running from
1855 to 2002. It is also very broad, including non-scientists such as Friedrich
Engels [No physiology is held to be scientic if it does not consider death an
essential factor of life. . . . Life means dying. From Dialectic of Nature (3)] and
unusual denitions, such as: Life is a system which has subjectivity.
Popa himself says that his list of lifes denitions serves only a general biblio-
graphic purpose, and he cites four bibliographies and discussions of denitions
of life that he says are more extensive than his own. Would any new insights be
gained by doing a similar analysis of more rigorous bibliographies of the deni-
tions of life, such as the four cited by Popa? Would it make sense to weight recent
denitions of life more heavily than older denitions of life, given that we have
learned much about life in recent decades? For example, in 1944, when Erwin
Schroedinger wrote his book, What is Life? (4), he predicted that life will be found
working in a matter that cannot be reduced to the ordinary laws of physics.
Life is Self-Reproduction with Variations. This consensus denition of life
from Trifonovs paper (1) is reduced to only two concepts Self-Reproduction
and Variation. It contrasts with the often-used denition from a panel for NASA
(National Aeronautics and Space Association): Life is a chemical system capa-
ble of Darwinian evolution. (5) In a paper based on this denition, Benner (6)
explains how reproduction with variation is not an acceptable denition of life,
because crystals grow, incorporating defects; and they reproduce when powdered
and used to seed the growth of more crystals. What crystals lack is heritability, as
in Darwinian evolution.
Perhaps a better denition of life would be, Self-reproduction with heritable
variations. In Popas 90 denitions, I nd only about 17 instances that might
be related to heredity, by summing the following search results: heritable, hered-
ity, hereditary, genetic, anagenetic, genome, mutation, and Darwinian. Perhaps
there are other relevant search terms that I have not thought about, or perhaps
heritability is simply not a common concept for dening life.
What about viruses? There is good reason to argue that viruses are living para-
sites that are capable of reproduction but not self-reproduction. This classication
Helen Greenwood Hansma
E-mail: hhansma@physics.ucsb.edu (or)
helen.hansma@gmail.com
Helen Greenwood Hansma
Department of Physics, University of
California, Santa Barbara, CA 93106
622 Hansma
of Viruses as Living is consistent with Trifonovs linguistic
analysis, in which there are 25 instances of reproduce/repro-
duction/replication but only 5 instances of self-reproduction.
Whether or not viruses are alive, they are clearly on a con-
tinuum between Living and Non-Living. The existence of
such a continuum complicates the search for an all-purpose
denition of life.
Do we need an all-purpose denition of life? On one hand,
Dyson writes an entire book, Origins of Life (7), without
explicitly dening life. Origins-of-life researchers do not nec-
essarily need a denition of life. For example, when I write
about the possible emergence of life between mica sheets (8),
I am hypothesizing about a wide span of events from non-
living to living. On the other hand, Hazen (9) says scientists
crave an unambiguous denition of life.
In response to the problem of dening life, another 2011
paper (10) uses quite a different approach. This paper rejects
altogether attempts to dene life, saying that the concept
of life is impossible to dene and is thus a metaphysical
concept instead of a scientic concept. The proposed solu-
tion is to use origin of evolution instead of origin of life.
Evolution, it says, may be dened by as few as three con-
ditions: [1] the emergence of open non-equilibrium struc-
tural systems, [2] self-replication, and [3] the acquisition of
heritable structure/function properties. Self-replication is
comparable to Trifonovs self-reproduction, though replica-
tion is perhaps a worse term, because it is typically used to
describe the copying of genetic material, which is only one
element in the reproduction of an organism.
Origin of Evolution is especially problematic, given the use
of evolution in other contexts, such as cultural evolution,
evolution of language, and evolution of the airplane. One is
left with the question, Origin of Evolution of What? In fact,
a new scientic subeld is the evolution of minerals. (11)
Life and minerals have co-evolved, according to Hazen, who
states that the earth had ~1500 minerals before the origin of
life, increasing to ~4300 minerals today, most of which may
be the result of biochemical processes. The origin of evolution
might thus be said to start when the biogeochemical processes
started during the process of the origin of life.
One of the biggest needs for a denition of life is in the eld of
exobiology. What does one look for, when seeking evidence
for life on Mars, for example? We know about life on earth,
but what about life as we do not know it? Trifonovs paper is
clearly useful for determining whether life has been created
in vitro, as he describes in his paper, that cross-replicating
ribozymes (12) evolve but do not replicate. Does Trifonovs
paper help those who are searching for life on Mars? Probably
not. Benner (6) addresses this problem by going beyond the
denition of life and into a range of questions, such as, Does
life require carbon? And, does life require water? Regarding
the rst question, the response is that carbon forms stronger
bonds than silicon, but only about one-third stronger.
In summary, Trifonovs paper is not the nal answer to the
question of what is life. It is, however, a brilliant approach
to the problem of giving scientists and non-scientists an
unambiguous denition of life.
References
R. Popa. 2. Between Necessity and Probability: Searching for the
Denition and Origin of Life. Adv Astrobiol Biogeophys (Springer-
Verlag, Berlin, 2004), pp. 197-205.
R. Popa. 3. Between Necessity and Probability: Searching for the
Denition and Origin of Life. Adv Astrobiol Biogeophys (Springer-
Verlag, Berlin, 2004), pp. 227-252.
E. Schroedinger. 4. What is Life? & Mind and Matter (University Press,
Cambridge, 1944).
G. F. Joyce. 5. In Origins of Life: The Central Concepts, in D. W. Deamer
and G. R. Fleischaker (Eds.), (Jones and Bartlett, Boston, 1994).
S. A. Benner, A. Ricardo, and M. A. Carrigan. 6. Current Opinion in
Chemical Biology 8, 672-689 (2004).
F. J. Dyson. 7. Origins of life. (Cambridge University Press, Cambridge
[England]; New York, ed. Rev., 1999).
H. G. Hansma. 8. Journal of Theoretical Biology 266, 175-188 (2010).
R. M. Hazen. 9. Genesis: The Scientic Quest for Lifes Origin. (Joseph
Henry Press, Washington, DC, 2005).
M. Tessera. 10. Int J Mol Sci 12, 3445-3458 (2011).
R. M. Hazen, 11. et al., American Mineralogist 93, 1693-1720 (2008).
T. A. Lincoln and G. F. Joyce. 12. Science 323, 1229-1232 (Feb. 27, 2009).
623
Comment
Life: Self-Directing with Unlimited Variability
on Self-Speeding
In his recent report in this journal, E. N. Trifonov (1) suggests that life should be
dened as self-reproduction with variations, based on a vocabulary analysis of
previous denitions of life. The method is novel, and the conclusion is interesting.
However, there are some problems in the analysis process, and the nal assertion
of the denition of life needs more cautious and deeper consideration.
The initial analysis, especially concerning the nine word groups (so-called
denientia), is impressive, which in some degree could reect peoples
common views up to now on the essential meaning of life phenomenon. This
analysis leads to a collective denition of life as metabolizing material infor-
mational system with ability of self-reproduction with changes (evolution),
which requires energy and suitable environment (referred to as denition [1]
in the original paper).
As the author says, this collective denition, though comprehensive, should be
worked on to reach a more concise one. This work is important because a satis-
fying denition should not be a collective one. However, the author does this
work in a way of some curtness. For example, it is mentioned that metabolism
implies both energy and material supply which also represent environment.
Though this seems true, on the purpose of taking out the words energy, mate-
rial and environment from the list, the author should say more than just one
sentence, especially considering metabolism is a word with quite different
interpretations. Furthermore, it seems that self-reproduction (replication)
implies metabolism as well needs a more detailed explanation rather than
the self-reproduction can proceed only on condition that metabolism are
in place. Instead, in a view of replication (reproduction) rst in the origin
of life (e.g. 2, 3), a contrary statement could be expressed as metabolism can
proceed only on condition that self-reproduction are in place, because enzyme-
like functional molecules have to appear by chance again and again if they could
not be produced in a self-reproduction system. If it is considered that metabo-
lism does not need functional molecules complicated enough like enzyme but
only simple ones, for example, produced in some assumed chemical autocataly-
sis reactions, then again, the meaning of metabolism needs more explanation in
detail. In fact, approving the view of replication (reproduction) rst, I agree to
the taking out of metabolism from the list, but not because self-reproduction
implies metabolism is already in place, instead, because metabolism could
be a thing derived from self-reproduction during evolution. Certainly, the
sentence the complexity (information) can be considered as product of
*Corresponding author:
Wentao Ma
E-mail: mwt@whu.edu.cn
Wentao Ma*
College of Life Sciences,
Wuhan University, Wuhan 430072,
P.R. China
624 Ma
self-reproduction with change (evolution), on the evolution-
ary route from simple to complex seems enough to justify
the taking out of complexity (information) from the vocab-
ulary list.
Based on the denition life is self-reproduction with varia-
tions (referred to as denition [2] in the original paper), if
variations is considered as a word equivalent to evolution (as
the author mentioned), along the logic line above, the nal
word left seems to be evolution. Apparently, evolution
can proceed only on the condition that self-reproduction is
already in place. Then, the most concise and conclusive def-
inition should be life is evolution, or more explicitly life
is something capable of (Darwinian) evolution, similar to
some early suggestions (see 4, 5 for reviews).
However, this is apparently not a satisfying denition,
because Darwinian evolution is per se a collective concept,
only appearing as a concise expression. In other words, we
still need to know what kind of things is capable of Darwin-
ian evolution. In fact, seeking a concise expression should
not be the only criterion to construct a satisfying denition.
A clear denition should catch the most fundamental mecha-
nism underlying the corresponding phenomenon. Therefore,
the denition life is self-reproduction with variation should
be appropriate but variation does not equal to evolution,
instead, it is a feature accompanying self-reproduction
which, together with the latter feature, leads to Darwinian
evolution.
As a further consideration, however, we should notice that this
denition remains not satisfying, because self-reproduction
is a word typically used in the life science (biology), and
should not be used to dene life unless we admit that there
is some special rule for the life phenomenon over other phe-
nomena in nature. In other words, we still need to know how
things could self-reproduce in nature. In a recent report of ours
(6), self-reproduction (replication) is explained in a chemical
background. The main conclusions are: rst, self-reproduction
(replication) in the substantial world could not mean others
but an entity favors the production of its own; second, the
major chemical mechanism for such favoring is catalysis,
which could be classed into the speed-favoring catalysis and
the direction-favoring catalysis (e.g. the enzyme-like function
is a speed-favoring one and the template-directing function
is a direction-favoring one); third, correspondingly, self-
reproduction could be either favoring its own production in
speed (self-speeding) or favoring its own production in direc-
tion (self-directing), or a combination of them.
Let us talk about some scenario in the origin of life to explain
these concepts. Life is very likely to have begun with RNA
(or RNA-like) molecules (the RNA world hypothesis) (7, 8).
Any RNA molecule could direct the chemical reactions
of nucleotide-joining to produce its own species via an
intermediate complementary sequence, under the mecha-
nism of template-directing copying by base-pairing. That
is self-directing. However, only some RNA molecules with
characteristic sequences might spread in a pool of random
RNAs in the competition for the limited common raw materi-
als, due to their enzyme-like function (so-called ribozyme)
favoring the self-directing process. Examples could be repli-
case ribozymes (catalyzing the template-directed copying) (8),
nucleotide synthetase ribozymes (9), etc. That is self-speed-
ing. It is just natural selection that works in this evolution,
and would further work on further evolution, selecting for
more or higher self-speeding features, upon the prereq-
uisite that different characteristic sequences with these
Figure 1: The scheme of the authors logic (above the dashed line) and my further considerations in this comment (below the dashed line) concerning the
denition of life. (A) Constructing the collective (consensus) denition according to the list of common words. (B) Constructing the concise denition by tak-
ing out redundant words. (C) Constructing the most concise and conclusive denition along the authors logic. (D) Spreading out the meaning of (Darwinian)
evolution to construct a clearer denition. (E) Spelling out the meaning of self-reproduction in a chemical background to construct a denition closer to the
essence of life in nature.
Life: Self-Directing with Unlimited Variability on Self-Speeding 625
features might appear by variation (in template-direct copy-
ing with some errors or other events, such as recombina-
tion). In modern life, DNA/RNA is the molecular base of the
self-directing and RNA/protein is that of the self-speeding.
We could image a bacterium as an entity absorbing raw
materials to construct its own offspring (self-directing),
in which process a lot of enzymatic reactions occur (self-
speeding). When a variation on the self-directing (originat-
ing as the change of its genetic information) appears and if
this variation could cause the change of the self-speeding
(manifesting as the change of enzymatic efciency or other
phenotypes), Darwinian evolution might take place.
If it is emphasized that the Darwinian evolution should be
ongoing forever, or say, with an open end (5), the variation
of heredity should be unlimited (10), carried by molecules
like DNA/RNA or similar polymers, and the corresponding
variation of phenotypes should also be unlimited, carried by
molecules like RNA/protein or similar polymers.
Then the denition should run in such a way as living things
are self-directing species with unlimited variability on self-
speeding or more concise life is self-directing with unlim-
ited variability on self-speeding. This denition includes
considerations on the chemical base of self-reproduction and
implies the most conclusive feature of life, i.e. Darwinian
evolution. A scheme of the authors logic and my further
considerations in this comment concerning the denition of
life is shown in Figure 1.
Acknowledgements
Financial support by the National Natural Science Founda-
tion of China (No. 30870660, 31170958) and the National
973 Basic Research Program of China (No. 2010CB530500,
2010CB530503) is gratefully acknowledged.
References
F. A. Anet. 2. Curr Opin Chem Biol 8, 654-659 (2004).
A. Pross. 3. Orig Life Evol Biosph 34, 307-321 (2004).
P. L. Luisi. 4. Orig Life Evol Biosph 28, 613-622 (1998).
K. Ruiz-Mirazo, J. Pereto, and A. Moreno. 5. Orig Life Evol Biosph 34,
323-346 (2004).
W. T. Ma, C. W. Yu, W. T. Zhang, P. Zhou, and J. M. Hu. 6. Theory
Biosci 130, 119-125 (2011).
W. Gilbert. 7. Nature 319, 618 (1986).
G. F. Joyce. 8. Nature 418, 214-221 (2002).
W. T. Ma, C. W. Yu, W. T. Zhang, and J. M. Hu. 9. RNA 13, 2012-2019
(2007).
E. Szathmary and J. M. Smith. 10. J Theor Biol 187, 555-571 (1997).
627
Comment
Classifying the Properties of Life
In his paper Vocabulary of Denitions of Life suggests a Denition, professor
Trifonov (1) analyzes the vocabulary of 123 existing denitions of life in order
to provide a path for nding a possible minimal agreement among scientists. To
this purpose, he compares from a linguistic point of view the denitions provided
in different accounts of life and ranks the terms used therein according to their
frequency. He then selects the most used words, which should also reect the
most accepted concepts about life, and groups them under generic concepts rep-
resenting their common general properties (or meaning). For instance, matter
represents the class under which molecules, organic matter and materials
fall. Finally, he reduces the conditions that the most frequently occurring deni-
entia represent to the states of affairs or events that require them. In this fashion,
for example, energy and material supply are included in the concept of
metabolism, while self-reproduction comprises also its essential conditions,
metabolism, system, energy and material supply. The outcome of this
analysis is a denition of life as self-reproduction with variations. This deni-
tion is claimed to be minimalistic for two reasons. First, it is a kind of minimum
denominator of the denitions taken into consideration. Second, it is applicable
to the minimal structures that can be involved in the origin of life. Moreover,
the minimalistic denition is maintained to be generic, as it provides a unique
common basis for all varieties of life, including extra-terrestrial life, computer
models and abstract forms. However, this proposal raises two crucial questions.
Is self-reproduction with changes a good denition? Can this denition actually
provide a minimal basis of consensus?
One of the Possible Denitions of Life
The purpose of a minimalistic denition of life is to reach a minimal consensus.
As Trifonov acknowledges (1), there are more than 100 denitions of life, and
many of them conict with each other. The minimalistic denition captures the
list of the most recurring dening terms, based on the assumption that recurrence
reects acceptance. A problem with this proposal can arise from the assump-
tions underlying the grouping of the characteristics and their reduction to generic
properties or more complex phenomena. A hypernym semantically includes hyp-
onyms, but this does not correspond to the fact that who accepts a more specic
concept is also willing to accept a more generic one, especially when the choice
amounts to exclude a distinguishing property. Moreover, more complex states
of affairs or events can include more generic concepts or precedent or essential
conditions, but causal precedence does not correspond to a logical or an epistemic
necessary condition. The effect of this double process of reduction is a denition
of life that risks incurring the same problems of the criticized Darwinian de-
nitions (including their chemical and biological variations) (2, 3), characterized
by the same characteristics of self-reproduction and variation. As Zhurav-
lev and Avetisov (4) put it, these characteristics are excessively discriminatory,
Fabrizio Macagno
E-mail: fabrizio.macagno@fcsh.unl.pt
Fabrizio Macagno
Instituto de Filosoa da Linguagem
(IFL), Faculdade de Cincias Sociais e
Humanas, Universidade Nova de
Lisboa, Avenida de Berna, 26-C,
P 1069-061 Lisboa Portugal
628 Macagno
as on this perspective it is hardly possible to specify life,
including early life, before the emergence of the replication
machinery. Moreover, sterile beings such as mules should
be excluded from the forms of life (5). Finally, the very con-
cept of self-replication is one of the most controversial mat-
ters in the research on the origin of life, or rather minimal
life. As Luisi (6) put it:
Even with the simplication of minimal life and way sta-
tions, it is clear that the process leading to life is a contin-
uum process, and this makes an unequivocal denition of
life very difcult. In fact, there are obviously many places
in Oparins pathway where the marker minimal life
could arbitrarily be placed: at the level of self-replication;
at the stage where self-replication was still accompanied
by chemical evolution; at the point in time when proteins
and nucleic acids began to interact; when a genetic code
was formed, or when the rst cell was formed.
The decision of choosing the two characteristics of self-
replication and variation can lead to controversies about the
necessary condition of the denition, making it more specic
and less general than many approaches to life origin require
(7). Moreover, the denition can be also controversial from
the point of view of the sufcient conditions. The denition
mentions an activity (self-replication) but does not specify
any quality that the agent, or rather the logical argument,
needs to satisfy. As a result, life simulations can be classi-
ed as actual forms of life, as claimed by functionalists who
regard life as an abstract process. However, this theoretical
position, implicitly supported by the rst Darwinian deni-
tions (8), has been strongly disputed (2). The risk with this
minimalistic denition is the failure to meet the essential
logical requirement of a denition, its convertibility with the
deniendum (5, 9), or rather, if we consider other scientic
approaches to this logical conditions (4), its being univer-
sal and minimal and specic enough.
Denitions and Methods of Denition
The collection of the properties commonly included in the
existing denitions of life and their reduction to a minimal
description can be hardly accepted by the different approaches
to the problem of life (5). Moreover, the choice of a denition
of a controversial concept counts as an implicit support to a
specic theory (6), or more generally speaking, a potentially
controversial viewpoint (10).
This issue becomes much more complicated if we consider
that not only are denitions fundamental for nding a theoreti-
cal agreement, they are also essential for classifying entities.
A genus-difference denition cannot be effective for distin-
guishing between living and non-living beings in space or on
other planets (5, 11), while an operational denition cannot
provide a theoretical ground for the origin of life (12). Ranking
the properties according to their frequency can be helpful for
showing their degree of acceptability. However, such a princi-
ple can be combined with other criteria not only hinging on syn-
onymy or causal inclusion. For instance, Kompanichenko (7)
started from a similar collection of denitional properties and
then selected the fundamental ones based on their discrimi-
nating power, or rather their usefulness for the purpose of
distinguishing between categories. For instance, accumula-
tion of free energy was chosen because it, better than other
properties, allowed one to discern between active and passive
systems.
This systemic account is different in method and purpose
from Trifonovs one, as it is only aimed at providing a possi-
bly shared biological denition of life. However, it points out
two methodological dimensions that can be seriously taken
into consideration in the classication of denitional proper-
ties. The rst one is the selection of the kind of denition, and
consequently the choice of the concept to be dened (13). The
second is the grouping of the properties according to their
denitional purpose. The type of denition, or better the de-
nitional sentence, is materially related with the purpose of the
denition itself. Ancient dialecticians distinguished between
fteen types of denitions (14), of which the most power-
ful from a logical point of view was the method of genus-
difference. The so-called essential denition was the only
one that at the same time guaranteed the convertibility between
deniens and deniendum and provided a description of the
fundamental semantic properties of the concept dened (9,
15). Modern scientic theories rely on similar types of de-
nitional methods (13), plus the operational (unmentioned in
the ancient treaties) and the implicit denition (16-18), which
cannot be properly considered as descriptions of the denien-
dum. All such denitional methods rely on the distinction
between the semantic-logical properties of the predicates:
the semantic categories (such as substance, having, doing...)
and the logical predicables (such as the genus-species or acci-
dental relation between predicates). For instance, life is a
noun abstracted from the predicate to continue, to live (19),
therefore denoting a state of beings, or a property thereof, but
not a substance, matter or entities, which can rather differenti-
ate the biological living state (condition of chemical systems,
as stated in some Darwinian denitions, see 6) from computer
simulations. Some properties, as the ones used in operational
denitions, (3) can be simply accidental, namely can charac-
terize some forms of life, such as life on earth (11).
Conclusion
The denition of life drawn from the analysis of the proper-
ties listed in the existing denitions opens new possibilities
of research. One of them consists in applying classical meth-
ods of property classication in addition to the frequency cri-
terion. On this view, properties will be grouped according to
Classifying the Properties of Life 629
their logic-semantic features characterizing their deni-
tional role. Such properties can be then selected according
to their statistical acceptability or hypernymy (or rather
genus-species) relations. Moreover, depending on the differ-
ent purposes of the denition (and denieda) it is possible
to formulate different potentially shared minimal denitions.
The choice of alternative property classication criteria (for
instance, semantic traits or observable properties) can make
it possible to provide different statistically minimal kinds of
denition, adequate for and aimed at distinct purposes.
References
C. Cleland and C. Chyba. Does Life Have a Denition? 2. .
In Sullivan, W. and Baross J. (Eds.), Planets and Life: The Emerging
Science of Astrobiology (119-131) Cambridge: CUP (2007).
C. Cleland and C. Chyba. 3. Orig Life Evol Biosph 32, 387-393 (2002).
Y. Zhuravlev and V. Avetisov. 4. Biogeosciences 3, 281-291 (2006).
J. Oliver and R. Perry. 5. Orig Life Evol Biosph 36, 515-521 (2006).
P. Luisi. 6. Orig Life Evol Biosph 28, 613-622 (1998).
V. Kompanichenko. 7. Frontier Perspectieves 13, 22-40 (2004).
C. S 8. agan. Life. In Encyclopdia Britannica (2007).
Aristotle. Topica. In Ross W. D. (Ed.), 9. The works of Aristotle.
Oxford: Oxford University Press (1969).
E. S 10. chiappa. Dening Reality. Denitions and the politics of meaning.
Carbondale and Edwardsville: Southern Illinois University Press
(2003).
C. Chyba and C. Phillips. 11. Orig Life Evol Biosph 32, 47-68 (2002).
G. Bruylants, K. Bartik and J. Reisse. O 12. rig Life Evol Biosph 40,
137-143 (2010).
C. Malaterre. 13. Orig Life Evol Biosph 40, 169-177 (2010).
M. Victorini. 14. Liber de Denitionibus. Frankfurt: Peter Lang (1997).
F. Macagno and D. Walton. 15. Argumentation 23, 81-107 (2009).
P. Bridgman. 16. The Logic of Modern Physics. New York: MacMillan
(1927).
W. Dubislav. 17. Die Denition. Leipzig: Meiner (1931).
H. Dubs. 18. Philosophical Review 52, 566-577 (1943).
W. Skeat. 19. The Concise Dictionary of English Etymology. Ware:
Wordsworth Editions (1993).

631
Comment
Dening Life: Products or Processes?
Trifonovs study of the language used to describe living systems (1) is an eye-
opening glimpse into the assumptions underlying much of origins of life research
today. Unfortunately, for someone with a putative interest in words, Trifonovs
attempt to create categories of words often suffers from a lack of sensitivity to the
precise meanings of words, as becomes evident in the meta-categories he invents
for analyzing his ndings. Evolution and change are not the same thing as any
embryologist will tell you. Many things change without evolving. Any physicist
would cringe to see force subsumed under energy: The equation f 5 ma has
no energy term! These misunderstandings are not, of course, all Trifonovs, but
undoubtedly represent fundamental problems in how biologists misunderstand
the principles applicable to describing living processes. Such misunderstandings
are themselves troubling.
Unfortunately, these misunderstandings extend beyond words to fundamental
principles as well. Trifonovs denition of life as given by Darwin and Oparin are
both incomplete and misrepresent both mens actual theories. Darwinian evolu-
tion requires not just reproduction with variations or replication with mutation
but also critically! non-random selection. If there is no selection or selection
is random, there can be no evolution. Discovering the selection processes operant
during prebiotic evolution is an unexplored area of great importance.
A second major problem with Trifonovs approach, which to be fair is inherited
by him from his sources, is that it focuses on properties instead of processes. The
problem of understanding life is not simply describing a system that can replicate
and evolve through non-random selection. If these criteria were sufcient, then all
human inventions evolve. Indeed, we even have AI systems which employ enti-
ties that can acquire computer resources, use them to replicate, change through
mutation, and be non-randomly selected. The real problem of understanding life,
as Darwin and Oparin understood full well, is how it evolved without a designer
or programmer. Thus, the issue of what characterizes the properties of a living
system is subservient to the problem of how to evolve such properties through
natural processes that existed before any of the properties unique to life had them-
selves yet evolved. Clearly, whatever this process was, it had to be employ a
series of bootstrapping steps in which each new form of organization was able to
perform newly emergent functions. Describing and testing such an emergent pro-
cess is a fundamentally different, and far more difcult, problem than describing
the characteristics of living systems that resulted from it (2-4).
Indeed, restating the problem as one of processes rather than properties yields
a very different set of criteria for what it means to understand life and conse-
quently a very different set of terms for describing it. Some of these criteria are
listed in the following table, which I published recently (5). Notably, very few of
Robert Root-Bernstein
Phone: 517-884-5039
E-mail: rootbern@msu.edu
Robert Root-Bernstein
Department of Physiology, 2174 BPS,
Michigan State University,
East Lansing, MI 48824, USA
632 Root-Bernstein
the terms in the Table occur in any of the lists summarized
by Trifonov, demonstrating how very different the process
approach to understanding life is as compared with the prop-
erties approach.
The processes approach to understanding life also sheds a very
different light on current attempts to engineer living systems.
We must remember that even in the building of human edi-
ces and inventions, we often make use of scaffolds that leave
no traces on the nal products they make possible. Imagine
trying to explain how to build a skyscraper without knowing
about cranes, bulldozers or cement mixers! Any account of
the evolution of life must leave open the possibility, and even
the likelihood, that life itself beneted from metaphorical
scaffolds that have long been discarded yet were essential
to permitting living organizations to emerge. So even if we
could manufacture in a laboratory each and every component
of a cell from its membranes to its metabolic machinery and
its chromosomes, and then mix these engineered components
together to produce a functional cell, this would tell us noth-
ing about how life evolved. Even if we keep deleting genes
until we reach some apparent minimum without which a cell
cannot function, this tells us nothing about how that minimal
set was elaborated, integrated, and selected from the set of
molecules and genes that nature elaborated on its random
walk toward life. So in dening life, we have to be clear about
why we want to dene life: is the purpose to be able to make
and modify life, or is it to understand how life itself came into
existence? Do we want to engineer lifes products or recap-
ture the processes of evolution itself? These are two very
distinct questions that will require very different approaches.
Unfortunately, too much of recent research in origins of life
has confused or even conated the two. Perhaps Trifonovs
study will prompt us to reconsider which questions are of
most interest.
References
R. Root-Bernstein and P. F. Dillon. 2. J Theor Biol 188, 447-479 (1997).
A. Hunding, D. Lancet, F. Kepes, A. Minsky, V. Norris, D. Raine, 3.
K. Sriram, and R. Root-Bernstein. Bioessays 28(4), 399-412 (2006).
V. Norris and R. Root-Bernstein. 4. Int J Mol Sci 10, 2611-2632 (2009).
R. S. Root-Bernstein. In: Busiak, V. and Navorro-Gonzalez, R. (Eds.), 5.
Astrobiology: From Simple Molecules to Primitive Life, American
Scientic Publishers, pp. 285-314 (2010).
633
Comment
Life?
Life! Needs a denition? Never thought about that.
Life! What is it? Been thought about since childhood and surely from times
immemorial.
Are these two questions same or different? That depends upon semantics.
In his paper (1), Trifonov has put forth a denition: Life is self-reproduction
with variations. He came to this denition as the minimal essential set through
a linguistic as well as mathematical Principal Components Analysis-like analy-
ses of a vocabulary of 123 tabulated denitions of life. This vocabulary depends
on the most frequent words used to dene life such as life, system, energy,
complexity, ability, reproduce among others.
This very easily comes to mind that it is the words exactly that have come to
Trifonovs aid in dening life. Shabd (Sanskrit/Hindi) 5 Word.
Ah! English, not to forget the good old Mathematics role in trimming down the long
list here. Does not matter whether the English is written or pronounced. It is said
that the primal sound Aum! or Om! is the rst word that a new-born child utters
immediately after being brought to life in the outside world and a few seconds before
the actual crying begins. Life forms other than human beings too have a way of com-
munication with each other and with human beings through sounds; that are words
in their context, but sounds for us humans. Nonetheless, a parrot can be taught to
speak words while humans can mimic sounds created by these other life forms.
The semantics, a context can change a words denition. Words can be consid-
ered a life form as well. A word likes to exist within the sphere of one particular
denition. Yet, along comes a context trying to change the poor words denition.
It is quite possible that because of its resistance to the change from its haven, its
changed meaning may be subtle. Take teaching or cheating as an example.
There is a variation in the sequence of alphabets in these two words. While in
preparatory school, one kid had probably never heard the word cheating. So,
whenever classmates would cry out for a child copying in the test, Madam, he is
cheating, he is cheating!, the kid would yell along He is teaching, he is teach-
ing!. Well, for one thing, this latter statement is also quite true, because the child
is teaching copying to others, of course. And so holds true for DNA sequence
variations as well, with the genetic code degeneracy coming to the rescue, leading
to a subtle change or even no change at all.
The gist is this: Changes do take place. But what endures is the invariant Nature.
Inspite of all the uxes, storms, landslidings, the earth retains its natural green
Seema Mishra
E-mail: smsl@uohyd.ernet.in
Seema Mishra
Department of Biochemistry, School of
Life Sciences, University of Hyderabad,
Hyderabad, A. P. India-500 046
634 Mishra
charm; the sky still reects the same blue colour even if
clouded by grey clouds once in a while. Inspite of RNAs and
proteins being among the few forms of genetic material passed
from generation to generation, DNAs continue to rule as the
major invariant ones.
If life is self-reproduction, then what happens when it becomes
a fossil? No possibility of self-reproduction is there. Yet, it
still continues to exist in museums. And in the memory. It
does not die.
Trifonov writes, One unforeseen property of the minimalistic
denition is its generality. It can be considered as applicable
not just to earthly life but to any forms of life imagina-
tion may offer, like extraterrestrial life, alternative chemistry
forms, computer models, and abstract forms. This is a nicely
philosophical statement. But what about the material things?
Material things such as a classical rose-wood rocking chair,
arent they beautiful and seeming to have a life of their own?
I dont consider material things as life-less, they are also one
of the many life-forms. They exist. But what about their abil-
ity to self-reproduce, would they be dead simply because they
cant?
When we undertake research, practically speaking, what is
it exactly that we want to do? To understand life and its
innumerable little secrets and quirks. If not, then why do
research at all? What is it that we are seeking then? As M.Sc
students, when we have extracted the DNA from its native
place, nothing matches the joy and wonder of seeing the
pure, white DNA strands entangled together forming a mesh,
just like the web of life. And then we want to know more
about how it all forms a beautiful tangled web of life. DNAs
and proteins working together in tandem, yet still left unde-
ciphered as to how exactly do they produce a life-form.
Trifonov further writes about the Creation of a bacte-
rial cell with chemically synthesized genome, ...However,
it should be considered as very much assisted replication as
it was provided with an initial natural cytoplasm. And about
nearly fully articial life-form created by Sol Spiegelman,
...This has been an assisted replication as well, since the exper-
iments have been performed in presence of natural replicase.
So, without the replicase and the natural cytoplasm, arti-
cial life creations would not have been possible.
This means that Trifonovs denition does not entirely t the
bill. And we have to nd an invariant notion in the denition
of life, if we want life to have an immortal denition. What is
that invariant notion then; springing from its source, owing
along and transforming everything that comes in its path and
returning to its source in an iterative cycle; which makes life
possible in terms of self-reproduction (ow) and varia-
tions (transformation)? A beautiful, soulful melody.
Let us look outside Science for a clue, a hint, an inspiration.
Just like Trifonovs vocabulary list, it is far easier to see
that a few words have remained that bind all the many life-
forms across continents, cutting across the barriers. These are
Love and Soul. No need to go through complex linguistic
and mathematical analyses to reach these two words. Further
search for the question that which of these two may represent
more rational denition led to this knowledge propounded in
Shrimad Bhagvad Gita (2):
Acchedyoyam adahyoyam
akledyososya eva cha
Nityah sarva-gatah sthanur
achaloyam sanatanah!
English Translation follows:
Sri Krishna said to Arjuna: This individual Soul is unbreak-
able and insoluble, and can be neither burned nor dried. The
Soul is everlasting, present everywhere, unchangeable,
immovable and eternally the same.
Can we, then, think of the replicase and the natural cyto-
plasm above as Soul which makes life come alive?
Over to the invariant notion of life, then. Life is Soul!.
References
Shrimad Bhagwad Gita, Chapter 2, Verse 24. 2.
635
Comment
Is A n11 Denition of Life Useful?
In his recent article in this journal, E. Trifonov (1) is in accordance with the
seeming consensus among the specialists in the search for the origin of life
(chemists, geochemists, biochemists, biologists, exo/astrobiologists, computer
scientists, philosophers and historians of science) that there is an obvious need
for a denition of life (2). However Trifonov conrms the amazingly high
number of denitions of life, leading him to reect that scepticism is mul-
tiplied by the above number, leaving almost no chance for new formulations
which, however, continue to appear (1). Then I have two main comments:
1. There is a major issue in the proposed new denition Life is self-
reproduction with variations from the analysis of the 123 tabulated
denitions of life: Trifonov claims that self-reproduction and changes
(evolution) are independent notions but they are not. First, evolution
and changes are not synonyms. Variations are not strictly required for
natural selection to operate and evolution to occur if there is a collection
of various populations of individual systems belonging to distinct lin-
eages that can be formed de novo: natural selection will be able to pick
amongst these distinct lineages and thus allow the collection of various
populations to evolve. Of course, if sporadic variations are possible in
some lineages and if these variations are heritable, then the number of
new emergent lineages would be much higher and the evolution much
faster. Second, evolution is a process that requires self-reproduction.
When considering the above collection of various populations it can
evolve by natural selection only if each lineage is self-reproducing.
More precisely, as a lineage is basically characterized by (at least ) a set
of common properties, the same set of common properties as that of
their parents must be reproduced in the descendents in order to maintain
the specicity of each lineage and the distinction between lineages and
thus allow natural selection to pick amongst lineages (3).
2. More fundamentally, scientically speaking, I do not think any denition
of life useful. I fully agree with some scientists who consider that there has
been a dramatic shift in the past years as the question of life is no longer a
search for principles of life but has been transformed into a historical issue.
The question is no longer What characteristics are found in organisms but
not in inanimate objects? but How were these characteristics progres-
sively associated within objects that we call organisms? (4). I agree also
that it is always possible that somehow, whether on this planet or another,
an abiotic factor with properties totally unknown to us will be able to gen-
erate a pattern indicative of evolution of natural selection. However, if
such a factor exists, the burden should be to explain why it is abiotic (5).
Marc Tessera
Phone: 133-6-86-46-60-94
E-mail: marc.tessera@wanadoo.fr
Marc Tessera
2 Avenue du 11 November 1918,
Meudon 92140, France
636 Tessera
Actually the concept of life is too vague and gen-
eral, and loaded with a number of historical, tradi-
tional, religious values (6). Although life is a useful
word in practice, it is not a scientic concept (7).
The concept of life is related to an indenable state.
Any denition of life is subjective and arbitrary as is
the boundary between living and non-living systems
or pinpointing the moment when non living systems
would have become living. For instance, saying that
virus or prions or vesicles with the capacity of evolv-
ing are living systems (or not) adds nothing more than
the denition of life one would propose. Finally the
statement that any such boundary or moment exists
is not falsiable: no experiment can be considered to
prove that it can be wrong. Therefore, as the distinc-
tion between living and non living systems is a matter
of belief and not science, it is not only hopeless but
useless to try to dene this indenable state related to
a metaphysical question (3).
By contrast the distinction between systems with evolvable
capacity and systems without is not so problematic. For exam-
ple, among known open far-from-equilibrium self-sustained
systems there are cyclones. Such systems have a rather com-
plex dynamic organisation which can only be maintained if
cyclones are provided continously with matter and energy
(i.e. warm steam water vapour) by the local environment (i.e.
the sea). The organisation of cyclones is relatively stable dur-
ing their relatively short span life (only a couple of days
on Earth, although the span of life of similar systems can
be much longer in some cases: e.g. the red spot of Jupiter
which is actually an anticyclone). Such systems did not evolve
in a Darwinian sense and the dynamic organisation of such
orderly vortex motion has been fundamentally the same since
ever. They cannot evolve in particular because they lack the
capacity of self-reproduction. There is at least one example
of abiotic open far-from-equilibrium self-sustained systems
which can self-reproduce: the experimental vesicles with
amphiphile bi-layer membranes. These vesicles can grow
and bud, a kind of self-reproduction (8-11). However such
vesicles cannot evolve because they lack heritable properties
independent of the local environment, i.e. independent of the
nature of the nutriments provided by the local environment,
and thus distinct self-reproducing lineages cannot emerge (3).
Only a collection of various self-reproducing lineages of indi-
vidual systems can be sorted by natural selection and thus can
evolve. Actually most of the so-called living systems appears
markedly different from inanimate systems because they are
the end-products of Darwinian evolution, i.e. a continuum of
changes spanning billions of years.
There is no point in attempting to dene life because of the
irreducible metaphysical aspect of the concept. Instead it
seems more appropriate to focus on the process of Darwinian
evolution as the source of the primordial ancestor on Earth
and presumably similar systems elsewhere. The consensus to
be reached in the quest for the primordial ancestor must be in
dening the minimal process that allows Darwinian evolu-
tion to emerge and persist.
References
S. A. Tsokolov. 2. Astrobiology 9, 401-412 (2009).
M. Tessera. 3. Int J Mol Sci 12, 3445-3458 (2011).
S. Tirard, M. Morange, and A. Lazcano. 4. Astrobiology 10, 1003-1009
(2010).
L. Chao. 5. BioScience 50, 245-250 (2000).
P. L Luisi. 6. The Emergence of Life: from Chemical Origins to Syn-
thetic Biology. Cambridge University Press: New York, NY, USA
(2006).
J. Gayon. 7. Orig Life Evol Biosph 40, 231-244 (2010).
P. L. Luisi, P. Stano, S. Rasi, and F. Mavelli. 8. Articial Life 10, 297-308
(2004).
S. Rasi, F. Mavelli, and P. L. Luisi. 9. Orig Life Evol Biosph 34, 215-224
(2004).
P. Walde. 10. Orig Life Evol Biosph 36, 109-150 (2006).
B. H. Weber. 11. Orig Life Evol Biosph 40, 221-229 (2010).
637
Comment
Thermodynamic Inversion and Self-Reproduction
with Variations: Integrated View
on the Life-Nonlife Border
The excellent work by Trifonov (1) adds to the discussion of extremely important
questions: What is life?, or What is the difference between life and nonlife?
At present these questions have acquired practical sense, in particular, due to
plural experiments on prebiotic chemistry and efforts to obtain an articial cell.
Where is the border between a non-living prebiotic microsystem and the simplest
living unit? In the origin-of-life eld these both types of systems are often fused
into the innitive term protocell, no border between them. The Trifonovs mini-
malistic denition Life is self-reproduction with variation, in my opinion, rep-
resents a profound insight into the foundation of life. It may serve as an important
criterion for the distinguishing an actually alive molecular structure/system, who
in the future will inevitably be obtained in laboratory conditions.
Some aspects of fundamental biology, Trifonov arises in his article, should be
discussed in more detail.
Denition of Life or Properties of Life?
There exist more than 100 denitions of life. Most of them are true but none
is comprehensive. In the opinion of the author of this comments life is such a
phenomenon that can not be embraced with an exhaustive denition. Due to this
reason, the author in his works (2, 3) deliberately did not give a denition of
life. Instead, four key biological properties were formulated on the basis of the
comparison of biological and non-biological systems: 1) the ability to concentrate
free energy and information; 2) the ability to exhibit an intensied counteraction
to external inuences; 3) expedient behavior; 4) regular self-renovation on the
various levels, including self-reproduction. The essence of the properties could
be expressed by the author in the following thesis (or denition): a living system
concentrates free energy and information using the ability to exhibit an intensied
and expedient reaction to external changes extending its own existence through
self-renovation. In fact, the above-mentioned set of four fundamental biological
properties provides more opportunities for investigation of the origin of life than
the single thesis. The authors goal consisted in consideration of the transition
nonliving living systems from different sides; for this purpose the integrative
consideration of several properties was preferable in comparison with a single
denition. As for the Trifonovs work, apparently, his goal is different: to provide
the most compact and objective denition through creative integration of previ-
ous efforts in this area. And this goal has been achieved by him.
V. N. Kompanichenko
E-mail: kompanv@yandex.ru
V. N. Kompanichenko
Institute for Complex Analysis of
Regional Problems, 4 Sholom Aleyhem
St., Birobidzhan 67016, Russia
638 Kompanichenko
Life-Nonlife Border
Trifonov emphasizes two independent notions: self-
reproduction and changes (evolution); they, actually,
exclude one another, as self-reproduction is exact copying,
no changes, while changes can not relate to exact copying
(1). These combined notions are considered by him as a
unique attribute of life, or the border between life and non-
life: all is life that copies itself and changes. According to the
authors inversion approach to the origin of life, the decisive
step in the transformation of prebiotic microsystems into the
simplest living units (probionts) took place due to the ther-
modynamic inversion, i.e. radical change of the balances
free energy contribution/entropy contribution and infor-
mation contribution/informational entropy contribution into
negative entropy values (2-4). The thermodynamic inversion
changes the direction of free energy, information and entropy
transfer in the interchanging processes between the micro-
system and its surroundings: free energy and information
start to be imported into the microsystem, while entropy is
exported outside. Simultaneously the exchange of substances
is reorganized to facilitate extraction from the surrounding
energy-rich compounds, providing molecules suitable for
constructing new structures in the microsystem. Since the
inversion, functional processes arose and connected the main
types of biopolymers sequences of nucleotides and pro-
teins. Unlike a polynucleotide or proteinoid chain articially
synthesized in vitro, a functional sequence is meaningful (5).
Functional sequences produce function at their destination
(binding site or ribosomal translation site). Algorithmic
optimization (selection of each symbol in the sequence spe-
cically for function) occurred in the course of internal circu-
lation of bioinformation, through continuous recombination
and selection. In this way the inverse prebiotic microsystem
becomes an active constituent with respect to the medium.
Simultaneously the environment becomes part of the physi-
cal medium that is being actively inuenced by life.
The Trifonovs denition and the authors origin-of-life con-
cept are two different approaches to understanding of distinc-
tion between living and non-living systems. In spite of the
difference between them, they can be integrated.
The Authors Interpretation of the Trifonovs Denition
Why are the two opposite attributes, self-reproduction and
changes, in the foundation of life, according to the Trifonovs
denition? How could they arise? A possible answer can be
found in the inversion approach to the origin of life (2-4).
The approach offers that thermodynamic inversion might
occur only in a prebiotic microsystem oscillating around the
bifurcation point under far-from-equilibrium conditions. In
the case of balanced oscillations the microsystem acquires
a bifurcate structure because of its intermediate position
between two attractors the initial and (potential) new states
(Figure 1). There appears a paradoxical organization sta-
bilized instability that preceded its transformation into the
living unit in the course of thermodynamic inversion. Oscilla-
tions of the microsystem around the bifurcation point are not
symmetrical: the forward transition over the bifurcation point
Figure 1: Spectrums of the potential states of a chemical system oscillating around the bifurcation point (in the course of nonequilibrium transition from the
initial stable state into advanced stable state through the unstable point of bifurcation). A trend to advanced higher-organized state; B trend to advanced
lower-organized state; C' and C'' reverse trends to the approximately initial state. On the left (from the bifurcation point) restricting spectrum 1 focused on
the initial state, on the right expanding spectrum 2 directed to the set of potential advanced states.
Thermodynamic Inversion and Self-Reproduction with Variations 639
brings new accidental change that reects in the expanding
spectrum of the potential advanced states (Figure 1, right
part). The back transition is characterized with the restricting
spectrum of the potential states because the system strives to
return closer to the initial state (Figure 1, left part). Continu-
ous oscillations lead to appearance of new and new changes
in the microsystem due to the expanding spectrum of forward
transitions; some of them are conserved in congruence with
the restricting spectrum of the back transitions. As a result,
such an oscillating prebiotic microsystem obtains two oppo-
site tendencies to conservation and modication, at the
same time. In the authors opinion, the compact Trifonovs
denition of life reects the consequences of prebiotic pro-
cesses on the early Earth.
References
V. N. Kompanichenko. 2. Int J Astrobiol 7, 27-46 (2008).
V. N. Kompanichenko. 3. Planet Space Sci 57, 468-476 (2009).
V. N. Kompanichenko. In: Seckbach, J. (Ed.), Genesis In The 4.
Beginning: Precursors of Life, Chemical Models and Early Biologi-
cal Evolution (Submitted to Springer, Dordrecht, NL, 2012).
D. L. Abel and J. T. Trevors. 5. Theor Biol and Med Model 2:29.
doi:10.1186/1742-4682-2-29 (2005).
641
Comment
Life in Its Uniqueness Remains Difcult
to Dene in Scientic Terms
Research on lifes genome and proteome and its possible origins is challenging
and fascinating. Dening life in scientic terms, however, remains a highly dif-
cult task. Over 100 denitions have been suggested in the course of generations
of philosophers and scientists and the list of denitions just continues to grow.
This points to an actual lack of a convincing consensus on the denition of life.
At the recent 17
th
Albany Conversation, June 14-18, 2011, New York, E. N.
Trifonov presented rst results of a unique linguistic word count analysis, per-
formed on the large corpus of all denitions of life. This carefully performed
statistical analysis suggested (1) that Life is self-reproduction with variations.
In his most recent report in this journal E. N. Trifonov (2) describes the analysis
of 123 tabulated denitions of life in high detail. Some of these denitions were
also discussed in a special issue of the journal Origins of Life and Evolution of
Biospheres (3) reecting on the difculties of dening life. E. N. Trifonov argues
that most of the denitions do have some shared common sense suggesting that
one could arrive to a consensus. Even if the different authors cannot be brought
together through space and time E. N. Trifonov organized a sort of voting in
absentia by statistically analyzing individual words used in the set of denitions.
The words most frequently used might according to Trifonov reect on their
importance, as shared by many of the authors. The careful analysis originated one
rst attempt for the word count generated denition of life. It goes like Life is [a]
metabolizing material informational system with ability of self-reproduction with
changes (evolution), which requires energy and suitable environment. This rst
life-dening attempt was discussed in the context of previous comparative lin-
guistic studies on the denition of life. E. N. Trifonov continued to search for
a more concise and shorter denition of life by extracting two terms from the
vocabulary of denitions. Trifonov concluded, as mentioned in the context of
the Albany Conference above, with the denition of life saying that life is self-
reproduction with variations. This denition can indeed be applied as a practi-
cal guide in topical origin-of-life research, for example on protocell formation
including the encapsulation and elongation of nucleotides (4).
Is this the ultimate and universal denition of life? Probably not. Take a self-
reproducing malicious software script like a computer virus, a computer worm,
or a Trojan horse. Computer viruses spread from one computer to another via
a network or via internet by reproducing themselves. After several hundreds of
copies (and infected computers) random variations will provoke that the latest-
generation offspring virus is not to 100% identical to the ancestor virus script.
A computer virus performs self-reproduction with variations. It is not alive.
Please note that variations observed in biological evolution such as mutations are
Uwe J. Meierhenrich
Phone: 133 (0) 492 076177
Fax: 133 (0) 492 076151
E-mail: Uwe.Meierhenrich@unice.fr
Uwe J. Meierhenrich
ICN, UMR 6001 CRNS,
University of Nice-Sophia Antipolis,
06108 Nice, France
642 Meierhenrich
non-directed variations. They are sudden, spontaneous, and
random changes (5, 6) that do not imply any driving force
other than dissipating energy.
What about other denitions of life? (Figure 1) Wikipedia,
for example, posts that Life is a characteristic that distin-
guishes objects that have self-sustaining biological processes
from those which do not. The difculty with this denition is
that it refers to biological processes. Biology as explained
by Wikipedia is dened as the study of life. Here we turn in
a circle. This is elegant but not helpful. Such as Your right is
where your thumb is left. I do not attempt to give a competing
denition of life here. Being physico-chemist I would pre-
fer denitions of life that incorporate lifes performance and
control of metabolism, including autocatalysis, cyclic kinetic
processes, feedback loops, and active transport. Because such
denitions may better help to detect and characterize life in
extraterrestrial and extrasolar planetary systems.
Interestingly, the linguistic analysis applied by E. N. Trifonov
for the denition of life is conceptually close to a method
known as Principal Component Analysis (PCA). PCA is a
mathematical procedure extracting the major (principal) com-
ponents covering most of the data for further statistical treat-
ment and analysis. As outlined by E. N. Trifonov (2) PCA
has been applied by himself (ENT) to decipher a consensus
on the temporal recruitment order of amino acids into early
proteins (7, 8). Further work should correlate the important
PCA-derived recruitment order of amino acids with experi-
mental data on the formation of amino acids for example in
the prebiotic atmosphere (9) and even in interstellar environ-
ments (10, 11).
References
E. N. Trifonov. 1. J Biomol Struct Dyn 28, 1060 (2011).
J. Gayon, C. Malaterre, M. Morange, F. Raulin-Cerceau, and 3.
S. Tirard (guest Eds.), Special Issue: Denitions of Life. Origins Life
Evol Biospheres 40, 119-244 (2010).
U. J. Meierhenrich, J.-J. Filippi, C. Meinert, P. Vierling, and J. P. 4.
Dworkin. Angew Chem Int Ed 49, 3738-3750 (2010).
P. Atkins. 5. On Being: A Scientists Exploration of the Great
Questions of Existence. Oxford University Press (2011).
U. J. Meierhenrich. 6. Angew Chem Int Ed 50, 9240 (2011).
E. N. Trifonov. 7. Gene 261, 139-151 (2000).
A. P. Johnson, H. J. Cleaves, J. P. Dworkin, D. P. Glavin, A. Lascano, 9.
and J. L. Bada. Science 322, 404 (2008).
G. M. Muoz Caro, U. J. Meierhenrich, W. A. Schutte, B. Barbier, 10.
A. Arcones Segovia, H. Rosenbauer, W. H.-P. Thiemann, A. Brack,
and J. M. Greenberg. Nature 416, 403-406 (2002).
C. Meinert, P. de Marcellus, L. Le Sergeant dHendecourt, L. Nahon, 11.
N. J. Jones, S. V. Hoffmann, J. H. Bredehft, and U. J. Meierhenrich.
Physics of Life Reviews 8, 307-330 (2011).
Figure 1: Wordle assembled keywords on the denitions of life.
643
Comment
Denition by Means of Indeniteness
Humans recognize themselves as a part of humanity, of the biological world and of
life simultaneously. They identify themselves differently in each case. However,
in the absence of an accurate denition of life, the process of the identication
of humanity remains incomplete. The incompleteness of this process justies the
numerous attempts to dene life. Nevertheless, none of these previous attempts
has been indisputably successful. This previous lack of success implies that life
possesses some elusive feature(s) escaping the (current) denition. In a recent
paper (1), Edward N. Trifonov tries to nd these features of life with a word
count approach. This work is akin to publications that analyze sets of published
denitions (see reference in ref. 1), but it differs from them in its level of gener-
alization. The denition obtained after such generalizations, is, I am afraid, only
loosely connected with the essence of life. Four comments below will illustrate
the reasons for my mistrust.
1. Concerning the approach. Any statistical analysis is fruitful if and only
if the sample is representative. In this case, there are two uncertainties:
whether the denitions for analysis were selected correctly and whether
the selected denitions actually include the principal features of life. Both
aspects are of importance because statistics cannot help to discover char-
acteristics absent from the sample. As I noticed above, the life possesses
some elusive feature(s) escaping the (current) denition so life cannot be
dened exhaustively at present time.
Statistical analysis (even if the second aspect of the problem, i.e., the con-
tent of the denitions, is incomplete) can be useful for studying the history
of scientic reections about life. However, the latter is not the purpose
of the work reviewed here. The goal of the work is to give a possible
shorter denition of life containing components that are both necessary
and sufcient. To achieve that goal, all the words from the 123 denitions
of life published at different times were considered, and the frequency of
these words was calculated (Table 1). The relative frequency of use of the
words was not considered in the subsequent analysis. Instead, the words
were combined in 10 groups according to their common meaning, and the
6
th
group was given further consideration. The author was clearly under
the impression that the 6
th
group was chosen on the basis of word count.
However, this group was clearly chosen on the basis of an evaluation of the
inclusive capacity (although no measure of capacity was presented in the
text) of certain arbitrarily selected words. All of the subsequent analyses in
the paper are unrelated to word counts.
2. Concerning the subject under consideration. In discussions of the deni-
tion of life, many authors use (explicitly or otherwise) the terms life and
Yuri N. Zhuravlev
E-mail: zhuravlev@ibss.dvo.ru
Yuri N. Zhuravlev
Institute of Biology and Soil Science,
Russian Academy of Sciences,
Far Eastern Branch, 159 100-letiya Ave,
690022, Vladivostok, Russia
644 Zhuravlev
organism as synonyms (2). This shortcoming can be
discovered in many of the 123 papers reviewed. Strictly
speaking, this shortcoming makes the exploitation of
the method of principal components unacceptable in
this case. This shortcoming explains (in part) the rea-
son that the denitions are more than often in conict
with one another (because different subjects were
treated). In the paper reviewed, the author avoids this
topic entirely. However, to disregard the distinction
between life and organism is a shortcoming of great
signicance. To interpret life as an organism means to
overvalue the genetic constituents of the system and to
underestimate all other features.
I hypothesize that a biological object cannot be exhaus-
tively dened solely in terms of its genetic constituents.
It is necessary to combine the internal and external de-
nitions of a biological object (3). The internal denition
is primarily genetic and considers the biological object
as a triad: O
int
5 (P, F, Ph), where p denotes program,
f functions and ph observables [see details in (3)].
The successions, recursions and compositions of map-
pings (on the basis of these three components) make the
object. The external denition reects the position and
role of the biological object in its surroundings (in unity
of living and non-living). Here, the object can be inter-
preted as a certain operator converting the surroundings:
O
ext
5 F:S
1
S
2
. This denition is more ecological.
Separately, no denition can be sufcient to dene a
biological object. However, both denitions, even if
taken together, are insufcient to dene life as a system
because the multitude of biological objects is only a list
of elements related to life, whereas the production of the
system from its elements introduces novel properties
that cannot be inferred directly from the characteristics
of the elements. Thus, the denition of life as a system
must include characteristics absent from the denitions
of biological objects. The potential innity of life (in
contrast to the nite nature of objects) is an example
of such novel characteristics. Again, this topic was not
addressed by the paper and that remains unclear what is
characterized through exact replication.
3. A comment regarding the attempt to improve Darwin.
The short Darwinian formula descent with modica-
tions, which Darwin used to ground the theory of ori-
gin of species (not the origin of life), was transformed
by the author into self-reproduction with variations.
Even if one pays no attention to the legitimacy of such
a transformation, a question remains: are the pairwise
substitutions reproduction/descent and variation/
modication (as a substitution of one versatile term for
another such term, where the content of the two terms
overlaps in part) fruitful in any sense? Here, the author
uses the term self-reproduction, which he explains as
exact replication of the ideal RNA duplex , thus
obtaining the denition that life is exact replication with
variation (non-exact). Generally speaking, the neolo-
gism self-reproduction lies beyond intuition and even
beyond second law of thermodynamics, but its content
(used in the paper) was not specied by the author.
As result, clear Darwinian formula was converted in
the vague vulnerable allegation in which nothing of
Darwinian formula was conserved.
4. The title of the paper, Vocabulary of Denitions
of Life Suggests a Denition, gives the impression
that the approach used was valid (almost without the
authors participation) to produce the conclusion that
all is life that copies itself and changes. I believe
that the author intervened in at least three principal
instances: rst, through the supposition (undoubtedly
incorrect) that the denitions considered include all
necessary and sufcient properties of life; second,
through the substitution of the word-count method for
a method of inclusive capacity evaluation; and third,
through the transformation of the Darwinian formula
[operating with natural selection and organic beings
(4)] into the denition of life [operating (here) with
undened subjects] and through subsequent gen-
eralization. This tangled and dashed line, by which
the author connected the word count results with the
meaningful laboratory experiments by Spigelman, can
be characterized as an operation of arbitrary treatment
but not that of compression whereas the latter opera-
tion is usually used in information theory to convert
a string in the shorter string (5). As consequence of
this arbitrary treatment, the image of the soap bubble
divided into two smallest bubbles is easily located in
the scope of the nal denition of life (as it is given in
the paper reviewed), but this waning image is inappro-
priate to recover the plethoric image of the biological
object or of that of life as a system.
References
Yu. N. Zhuravlev and V. A. Avetisov. 2. Biogeosciences 3, 281-291
(2006).
Yu. N. Zhuravlev and V. A. Avetisov. In: 3. Genetic Transformation,
M. Alvarez (Ed.), InTech, 29-52 (2011).
C. Darwin. Origin of species, John Murray, London (1859). 4.
P. M. B. Vitanyi and M. Li. 5. IEEE Trans on Inf Theory 46,
446-464 (2000).
645
Comment
The Denition of Life and the Life of a Denition
The meaning of life is probably of interest to any reective individual. However,
the denition of life is of interest to a smaller circle of researchers trying to better
elucidate the meaning of life in a reective, critical, and constructive manner. To
critically evaluate a novel denition of life one has to take a step backward and
understand the meaning of denition. In this context, I would like to draw what I
consider an interesting analogy between our understanding of measurement and
our understanding of denition. At the beginning of human civilization, measure-
ment took the form of a one-to-one correspondence between natural numbers and
pre-dened objects. Therefore, measurement was identied with the counting of
objects that exist, and I emphasize this point, prior to the measurement/counting
procedure. For instance, the ancient man could have counted his wives by using
his ngers in the same way as young children learn to count objects. However,
modern science has turned the idea of measurement on its head in the sense that
measurement is now understood as the operation through which we dene objects
whose existence cannot be trivially assured prior to the measurement process.
For instance, potential energy does not exist in a similar manner to ngers or
sheep. Potential energy as an object of scientic inquiry is operationally dened,
for instance, through the procedure of multiplying m, h, and g. Our understanding
of denition has been changed along the same line. Let me explain this argument.
Alchemy was obsessively involved with purifying the spiritual essence of mat-
ter the same as Plato was obsessed with purifying the essence of beings through
denitions. In retrospect, it seems that science has advanced not by purifying the
essence of objects, whether natural or conceptual, but by adopting the idea of
measurement/denition as (1) producing a novel object of contemplation (e.g.,
potential energy, imaginary numbers) and (2) pragmatically proving the benets
of this new measurement/denition.
With this context in mind, I would like to discuss Trifonovs interesting paper (1).
The paper is a highly intelligent attempt to dene life by purifying its concep-
tual gist from a corpus of denitions. This methodology is in line with current
attempts to harvest collective intelligence (2) for understanding the meaning
of a concept. In this case, the collective intelligence is that of the experts who
dened life. Revealing the most frequent terms in the denitions is a right step
in this direction. However, the frequency of terms may represent their base-rate
in language rather than their informational value in the context of the deni-
tions of life! This is the reason why raw frequencies are rarely used in automatic
text processing but other, weighted measures are used (3). Clustering the words
composing the denitions under different titles is not a trivial task, as the crite-
rion for clustering and the justication for using it should be stated. Trifonov
does not use a structured method for clustering but intuition only. Comparing
his results to those of Kompanichenko is of minor use in establishing the validity
Yair Neuman
E-mail: yneuman@bgu.ac.il
Yair Neuman
Department of Education, Ben-Gurion
University of the Negev, Beer-Sheva,
Israel, 84105
646 Neuman
of the clustering procedure, as Kompanichenkos data are
not a gold-standard and do not follow a strict clustering
procedure. In this sense, comparing the intuitions of two
researchers is of minor value for scientic validation as their
intuitions may converge while having nothing to do with the
real state of affairs. I must emphasize that I have nothing
against intuition, but one has to remember that the clustering
procedure used in this paper cannot pretend to have valid-
ity beyond intuition. Moreover, Trifonovs attempt to seek
components that are both necessary and sufcient cannot
be accomplished through the clustering procedure. Cluster
analysis, in its statistical sense and common scientic use,
does not support the identication of necessary and sufcient
features through which we may identify the essence of a con-
cept. In addition, we should remember that Wittgenstein has
already shown that different instances of a given concept do
not share a xed set of features that may be analytically used
for dening it. To recall, Wittgenstein coined the term family
resemblance (4) as a part of his attack on essentialism. The
idea behind family resemblance is that instances of a given
concept (e.g., Life) are united not by a single common den-
ing feature, but by a complex network of overlapping and
criss-crossing similarities. (5). For instance, living systems,
from the brain to the immune system and the fungi may be
generally characterized as meaning making systems (6).
However, the different expressions of meaning making do
not share the same features but criss-crossing similarities.
Based on the above critique, Trifonovs justications for the
process of clustering and extracting the components raise
some questions. For instance, why complexity (information)
is a product of self-reproduction with changes (evolution)?
Is self-reproduction with changes the cause of complexity?
In what sense? Lets take a simple case in which a string S1
comprised of letters from a nite predened alphabet is trans-
formed through copying + change into another string, S2. It
is trivial that for the long run, randomly shufing S1 would
result in the increase of entropy that might be mistakenly
interpreted as increased complexity. If the complexity of the
transformed string is genuine, what is the precise mean-
ing of the change through which the algorithmic complex-
ity of the string, for instance, increases? Can we argue that
the meaning of this complexity is necessary for dening the
meaning of the change and therefore complexity is not the
product of change but rather a necessary term for dening
it? These questions and many more pop up while reectively
contemplating Table II in ref. 1. The nal denition of life
self-reproduction with variations is economical and
impressive, and Trifonov concludes by arguing that the de-
nition is naturally required for the exploration and that it is
not a purely philosophical historical matter. Researchers in
biology are well familiar with the ideas of self-reproduction
and variation, and I wonder whether combining these compo-
nents in a minimalist denition of life produces a synergetic
effect. Lets return to the example of potential energy. While
h, m, and g are three trivial objects, their multiplication syn-
ergistically creates a new entity that can be further developed
(e.g., elastic potential energy, nuclear potential energy) and
used for measuring and understanding the physical world.
How can we use Trifonovs novel denition of life in guid-
ing us toward a better understanding of life? Answering this
question is a must in evaluating the potential benets of the
denition. Let me conclude my commentary by compliment-
ing Prof. Trifonov for addressing a fundamental question in
life sciences. Hopefully the questions raised in my commen-
tary may catalyze our understanding and the evolution of his
novel denition.
References
P. Levy. Collective intelligence. New York: Basic Books (1997). 2.
C. D. Manning and H. Shutze. Foundations of statistical natural 3.
language processing. Cambridge, MA: The MIT Press (1999).
L. Wittgenstein. Philosophical Investigations. Oxford: Blackwell, 4.
(1953).
H.-J. Glock. A Wittgenstein Dictionary. Oxford: Blackwell (1996). 5.
Y. Neuman. Reviving the living: Meaning making in living systems. 6.
Oxford: Elsevier.
647
Author Response
Denition of Life: Navigation through Uncertainties
I am pleased to receive such multifaceted response (1-19) to my paper (20). It
helped me to better realize what exactly I have done. Perhaps, the main thing
is original motivation: how from 123 uncertain denitions of the uncertain phe-
nomenon described in uncertain terms to derive a consensus, without engaging in
the debates, which so far did not bring the consensus. As P. L. Luisi put it: the
concept of life is too vague and general, and loaded with a number of historical,
traditional, religious values (21). The debates, therefore, have been intentionally
excluded from my analysis. No semantics, logics, semiotics, and alike, nor phi-
losophy in general were involved. With all respect to philosophy, mother of sci-
ences, I chose to keep away from it, with the risk of becoming non-scientic, and
engaged in the word-count approach, vocabulary method instead of insight (4),
which has never been tried for denition of life. The rst consequence, of
course, is an understandable avalanche of protests, but a comparable ow of
praise as well.
Thus, the main motivation and the main point of the disputed paper was to bypass
centuries-long philosophical debates on the denition of life, lacking the cohe-
siveness (13), which, as I see it, continue to lead nowhere, and suggest an entirely
new approach on a new ground, well away from the old territory. This point is
not appreciated by most of the comments dragging instead back to the weathered
grounds (1, 2, 4, 6-16, 18, 19). The risk with this minimalistic denition is the
failure to meet the essential logical requirement of a denition (8). Yes, indeed,
as it was not geared to the traditional routines of denitions.
Another intention in deriving the minimalistic denition was to nd, hopefully, a
practical guide towards potential minimalistic models of life. The resulting three-
word denition is considered by many as incomplete. A whole variety of deni-
entia to supplement it is offered: heritable variations (3), information, energy,
environment, thermodynamic inversion (5), error threshold (6), self-directing and
self-speeding (7), exchange with the environment, kinetics and self-assembly (11),
cell (11, 15, 18) (I do not consider cell as unit of life, see below), adaptive evolu-
tion (13), selection (14, 18), metabolism (16), lack of purpose, evolvability (18),
and Love and Soul (10). The last one deserves special comment. Following
Cartesian body/soul division I focused, as many others before, at the body (struc-
ture, mechanisms). The soul, as well as mind, consciousness, love remain rmly
in the philosophical and theological realm. Apart from additional dening words
full alternative denitions are suggested as well (e.g., 3, 4, 10).
Accepting the above suggestions would completely sterilize and smear the origi-
nal idea of the paper. A fable of S. Mikhalkov Elephant-painter suits here as
ironical metaphor. The elephants landscape painting was criticized by other
Edward N. Trifonov
Phone/Fax: 1972 4 828 8096
E-mail: trifonov@research.haifa.ac.il
Edward N. Trifonov
1,2
1
Genome Diversity Center, Institute of
Evolution, University of Haifa,
Mount Carmel, Haifa 31905, Israel
2
Central European Institute of
Technology and Faculty of Science,
Masaryk University, Kamenice 5,
CZ-62500 Brno, Czech Republic
648 Trifonov
animals for lacking Nile, and snow, and kitchen-garden (22).
The spectrum of the suggested additions to the denition also
vividly illustrates the starting point of the paper: derivation
of the consensus denition of life by the way of traditional
disputes leads only to further ination of the denitions and
to accumulation of disagreements.
The minimized denition fails to illustrate the myriad of
possibilities of lifes emergence (16). The minimized deni-
tion is not to illustrate, but to suggest what is common for that
myriad. Another comment is the question What is Life?
hardly can be considered scientic. Falsication is impossible
(6). But would not we still try to imitate life as close to its
essence as possible? Why should we surrender to Popperian
bounds, if current working hypotheses continue bring fruits
of new knowledge?
The philosophical disputes are often about terminology at the
expense of essence. Several comments are actually, termi-
nological (which term is better to use): Description instead
of denition (1), evolution instead of variation (7), processes
instead of properties (are not self-reproduction and mutation
both processes?), understanding instead of denition (14),
and other. Is it, really, important how exactly one or another
thing is called when a simple (nave some would say) com-
mon sense picture is to be drawn? Few self-explanatory words
are put together, describing what would be the target in the
search for minimal system/process/network/transition at the
border between life and non-life. The enchanting exercise
(2) of word count is meant as the way out of terminological
multinode net, to the simplest what to look for. The recipe,
whether right or wrong, should be minimalistic, and one such
recipe is offered. I hope that the denition suggested will be
useful in the search for the border, and I am glad that this
hope is shared, though not by all (see below).
I did abandon the rival grounds after suggesting the nine
denientia. They may serve as, again, a tentative minimal
set of relevant terms (notions, categories) to continue the
debates, perhaps, on more fruitful basis. I did so with some
curtness (7) since, after all it is not exactly my territory.
The suggested minimal denition is, obviously, debatable,
and the nal assertion of the denition of life needs more
cautious and deeper consideration (7). One possible out-
come is the construction with self-directing and self-speeding
(ibid). I suspect, however, that the debates would not go far
away from the minimalistic denition (if only one-two words
are added).
Lack of sensitivity to the precise meanings of words (14)
is common criticism. The 123 denitions are all fuzzy (2) in
various degrees. They emanate from enormity of the prob-
lem, and belief that only humble descriptions (1) may be sug-
gested. The vocabulary of the denitions is fuzzy as well,
often giving different names for the same thing, not mention-
ing the eternal disagreements what would be the meaning
of this or another word. The attempt to classify the words,
as in the disputed word-count paper, may only be fuzzy as
well as the concluding denition., as it is, indeed (7, 19), The
word force is good example (14). Strictly, it is not energy,
however, the only word group it may belong to is Energy.
After all, force is dv/dt, and v
2
is energy. Another example is
uncertain meaning of exact replication (19). Again, it may
belong, obviously, to Reproduction, rather than to any other
of the nine groups, irrespective of what exact meaning would
be given to it. Evolution and changes are not synonyms (17).
Yes, but the suggested groups of words with similar mean-
ings are not groups of synonyms. The clear Darwins
formula descent with modication (19) is as fuzzy as self-
reproduction with variations. Yet one more example of dif-
ferent understanding is derivative nature of complexity: it is
asked by one commentator why complexity (information) is
a product of self-reproduction with changes (evolution)? (12),
while according to another comment (7) it goes without ques-
tion: certainly, the sentence the complexity (information)
can be considered as product of self-reproduction with change
(evolution), on the evolutionary route from simple to complex
seems enough to justify the taking out of complexity (infor-
mation) from the vocabulary list. Viruses are in the strictest
sense incapable of self -reproduction (16). But the strictest
sense is avoided intentionally, otherwise none of the words of
the Reproduction group will go together. And no groups will
be formed at all.
One argument against the alleged redundancy of the minimal-
istic denition is that error-free replication (more precisely,
any information transmission process) is impossible (6).
This is clear case of misunderstanding: the variation in the
denition is meant, of course, as inherited propagated varia-
tion, not just error, that is mostly lethal.
Classication of denitional properties (8) is a whole universe
of uncertainties. Every single classifying word would invite
disputes. For example, does metabolism belong to Chemis-
try, or to Life, or to System? The most frequent words of the
vocabulary are life and living. Strictly speaking, they do
not belong to the same group of meanings, though common
sense (or intuition) would put them together. How to classify
the words without coming to absurd extremes of a denition
(all inclusive denition, or meaningless one-two word stumps,
like living matter, or system and environment)? By sug-
gesting those nine groups of related words I have taken a risk
to nd a golden middle that suits my intuition and common
sense. And I do have reasons to believe that it is close to the
intuition and common sense of many.
The end result of the anthropomorphic consensus polling(2)
nine or so word groups that could serve as denientia is,
Defnition of Life: Navigation through Uncertainties 649
essentially, there, no matter how accurately the groups are
gathered. Excessive sensitivity to precise meanings would
end, perhaps, in up to hundreds of word groups, to com-
pletely blur the target.
Is the denition so loosly constructed, vulgar for scholastic
perception, even non-scientic (e.g., 9, 16, 17), useful in any
way? Opinions divided. There are few on the positive side
(e.g. 1, 5, 6, 9, 12), while many disagree (2, 15-17). Does that
denition have a euristic power (6), and what it is useful for?
One opinion is the distinction between living and non living
systems is a matter of belief and not science, it is not only
hopeless but useless to try to dene this indenable state (17).
And How can we use Trifonovs novel denition of life in
guiding us toward a better understanding of life? (12). I
have not seen that efforts to dene life have contributed at
all to that understanding (J. Szostak, 15). Yet, the Szostaks
denition self-sustained chemical system capable of under-
going Darwinian evolution is broadly quoted. It, thus, has
something in it that appeals to researchers of life. Is not that
a manifestation of some better understanding? My own de-
nition helped me to realize, for example, that cell, probably,
would not be needed as part of minimal denition. Thus, the
efforts to imitate the minimalistic life, perhaps, do not have
to include the attempts to build the cell, as, say, in the work
of Szostak (23). As it is put correctly in (14), we have to
be clear about why we want to dene life: is the purpose to
be able to make and modify life, or is it to understand how
life itself came into existence? I thought of pursuing both
targets. In the process of construction of the minimalistic life,
hopefully, guided by the minimalistic denition, one certainly
will arrive to better understanding. The denition quite likely
has potential to yield genuine biological insights (6). This
denition can indeed be applied as a practical guide in topi-
cal origin-of-life research (9). An immediate concrete exam-
ple is recent experiment with synthesis of G
n
on template of
GCC
n
, checking whether G would be occasionally incorpo-
rated opposite G as well, thus, evaluating possibility of mis-
takes in the presumably ancient replication system (24). This
system based on GCC
n
has been suggested as the minimal
process (17) in (20 and references therein). The mentioned
work is part of an effort to design minimalistic system (pro-
cess) in accordance with the minimalistic denition.
Questioning the usefulness of the denition inevitably puts the
whole work under question. Indeed, some comments are rmly
negative (14, 19). Some, however, consider it as an important
contribution, resolutely so (1, 4, 5, 7, 12), or reluctantly (14).
At the same time a frequent motif is that the denition of life
is simply impossible (1, 5, 15, 19).
The methodology of the word-count work is, generally,
accepted with interest. The extreme negatives are given by
The ranking of words according to frequencies seems blind
to the underlying logical relationships (4), and There is no
genuine scientic justication behind this approach and no
guarantee that the numerous compared denitions are not all
based on common misconceptions (6). Yet it is delight-
fully clever, objective and quantitative approach to dening
life (3), and sound analytical effort applied rigorously on a
comprehensive body of literature (11). More moderate criti-
cism relates rather to suggestions on improvement: Trifonov
should not stop at the very rst principal component of his
statistical vocabulary ltering approach (2). This suggestion
is, unfortunately, unrealistic as the statistical ensemble for the
possible second component would be too small. Supplement-
ing the list of denitions by data from other sources would be
justied (3) but these data have to be not single individual def-
initions, like the one by V. Kunin (25), as suggested in (13).
I operated with known collections of denitions, which I did
not compile myself, not to get excessively biased. Property
classication should have been performed (8). Weighted
measures of information capacity of various words should be
used, and structured method for clustering rather than intu-
ition only (12). Inclusive capacity of the groups has not been
estimated (19). Attempt to seek components that are both
necessary and sufcient cannot be accomplished through the
clustering procedure (12). At this point I would disagree,
since the clustering was not used for that purpose in the
paper. Rather some straightforward (non-scientic!) intuitive
reasoning. The above suggestions are acknowledged and will
be considered in future work.
Several cases of the Is that life? category popped up in the
discussions.
Frost tracery on a window pane or frostwork-type miner-
alizations in cave deposits (2) is suggested as a non-life
example that ts to the denition. I would not agree with
this, since the replication of ice crystals shows variety of
shapes, but the same variety that does not change. Each
crystal type reappears unchanged. The indivisible pair self-
reproduction/variation, of course, implies that the variation
is copied in the next reproduction cycle. Thus, the state-
ment that self-reproduction without variation would be
entirely ctitious, in that it can never be realized as a natu-
ral process (2), is trivial. It simply says that every copying
is non-exact. But is the copying mistake always inherited?
Another example of the confusing non-life phenomenon
with life is the soap bubble divided into two smallest bub-
bles (19). There is no variation component in it, and it is
division, rather than replication. Sterilized cat and frozen
bacterium (4), as well as mules (8, 11) are just manifesta-
tions of life, or aberrant forms of life not a challenge to
any general denition. The fossil that continues to exist
in museums and in the memory does not die (10). But it
does not live either, as it does not make copies. On the
other hand, a computer virus performs self-reproduction
650 Trifonov
with variations. It is not alive (9). By my denition it is.
I thought that the two key features are applicable not just
to earthly life but to any forms of life imagination may
offer, like extraterrestrial life, alternative chemistry forms,
computer models, and abstract forms (20). Similarly, con-
sidering the generality of the denition it is wrong to state
that I pound on the RNA-world drum (13).
In conclusion, after reading the comments I realized that
although what I have done is not in the main stream of
research on denitions of life, and not fully justied method-
ologically, the result, as fuzzy as it is, and, thus, questionable
for some (but complimented by others) gives the tentative
self-explanatory concise answer to the questions what is that
we are all looking for, and what to do to get it, although
exact wording may need some brushing to become academi-
cally approved. The reader interested in the subject of den-
ing life and explaining its early evolution will nd sufcient
substance in (20) to make this article worth reading and
instructive (13).
I am grateful to all commentators, who joined my humble
efforts to move towards elusive target origin of life for
many suggestions and thoughts to contemplate. I hope to
continue the discussions beyond this time- and space-wise
brief exchange, as many questions remain unanswered.
References
E. Di Mauro. 1. J Biomol Struct Dyn, this issue
R. Egel. 2. J Biomol Struct Dyn, this issue
H. G. Hansma. 3. J Biomol Struct Dyn, this issue
G. A. J. M. Jagers op Akkerhuis. 4. J Biomol Struct Dyn, this issue
V. N. Kompanichenko. 5. J Biomol Struct Dyn, this issue
E. V. Koonin. 6. J Biomol Struct Dyn, this issue
W. T. Ma. 7. J Biomol Struct Dyn, this issue
F. Macagno. 8. J Biomol Struct Dyn, this issue
U. J. Meierhenrich. 9. J Biomol Struct Dyn, this issue
S. Mishra. 10. J Biomol Struct Dyn, this issue
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Y. Neuman. 12. J Biomol Struct Dyn, this issue
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M. Tessera. 17. J Biomol Struct Dyn, this issue
F. M. Yeong. 18. J Biomol Struct Dyn, this issue
Y. N. Zhuravlev. 19. J Biomol Struct Dyn, this issue
P. L. Luisi. 21. The Emergence of Life: from Chemical Origins to
Synthetic Biology. Cambridge University Press: New York, NY, USA
(2006).
http://www.youtube.com/watch?v=q44T40nuAAY 22.
S. S. Mansy, J. P. Schrum, M. Krishnamurthy, S. Tob, D. A. Treco, 23.
and J. W. Szostak. Nature 454, 122-125 (2008).
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