Insight Editions · No. 254
What Is Life?
How Chemistry Becomes Biology
Addy Pross
Pross answers Schrödinger’s question with a chemist’s theory: life is replicative chemistry, and evolution is the biological face of a drive toward dynamic kinetic stability.
A study guide to What Is Life? by Addy Pross. Shared free for personal reading; not for sale and not endorsed by the authors or publishers. Please read and buy the original.
The Book on One Page
Addy Pross, a physical organic chemist at Ben-Gurion University, answers Schrödinger's 1944 question with a chemist's theory: life is replicative chemistry, and Darwinian evolution is the biological face of a general chemical drive toward dynamic kinetic stability.
- The puzzle. Living matter is organized, purposeful, constantly turned over, diverse, far from equilibrium and homochiral. Maintaining such a state is thermodynamically legal; reaching it from downhill prebiotic chemistry is the mystery that troubled Bohr, Schrödinger, Monod and Popper, and molecular biology's triumphs have not dispelled it.
- The method. Understanding is pattern recognition, placing the particular inside the general, and reduction (holism being reduction with feedback) remains the only tool that works. Life's origin is a chemical problem, best attacked ahistorically: not "which molecules, where" but "why would any matter complexify toward life?"
- The key idea. Self-replication is autocatalytic and therefore exponential; populations of replicators can only persist like a fountain, by balancing formation and decay. That persistence is a second kind of stability, dynamic kinetic stability (DKS), in which the more reactive (better replicating) system is the more stable. Its selection rule, a Second Law analogue, moves replicators from less to more DKS.
- The unification. Test-tube replicators show selection (Spiegelman), niche partitioning (Joyce's RNA "finches") and cooperation (Joyce's cross-catalytic pair), so abiogenesis and evolution are one process. In chemical language natural selection = kinetic selection, fitness = DKS, information = specific catalysis, and the evolutionary sequence gains a step: replication, mutation, complexification, selection.
- The engine. A replicator that gains an energy-gathering capability can climb thermodynamically uphill while pursuing DKS; that, Pross suggests, is the moment life began, and it explains why every organism has a metabolism.
- The payoff. DKS explains life's six strange properties, dissolves Monod's paradox (kinetic directives look purposeful), recasts individuals as nodes in a replicative network, and implies that life must be synthesized step by step, like teaching someone to juggle one ball at a time.
| Ch | Title | One-line payload |
|---|---|---|
| P | Prologue | A working fridge in a field: life is a self-building factory that should not exist |
| 1 | Living Things are so Very Strange | Six properties of life that chemistry cannot yet explain |
| 2 | The Quest for a Theory of Life | From Aristotle to Monod, each revolution deepened the riddle; we need a theory, not a definition |
| 3 | Understanding 'Understanding' | Understanding is pattern recognition; holism is elaborate reduction |
| 4 | Stability and Instability | Autocatalysis creates dynamic kinetic stability, with its own selection rule |
| 5 | The Knotty Origin of Life Problem | Historical tools fail; both replication-first and metabolism-first hit the Second Law |
| 6 | Biology's Crisis of Identity | Genome-era biology, systems biology and non-equilibrium physics have not explained organization |
| 7 | Biology is Chemistry | One process from molecules to mammals; fitness is DKS; energy capture starts life |
| 8 | What is Life? | A definition, the six properties explained, and life recast as a network |
The Refrigerator in the Field
Sixty-five years after Erwin Schrödinger asked What is Life?, molecular biology can describe the cell in astonishing detail yet still cannot say what life is or how it arose from non-living chemistry. Pross frames the puzzle with a thought experiment, a working fridge found in an empty field, and announces his answer: a neglected kind of stability, dynamic kinetic stability, that turns Darwinism into one face of a wider chemical law.
The question that will not go away
The stakes are cosmic. If we knew how life relates to non-life we would know what we are and something new about the universe itself. Pross sets the two extremes side by side: the anthropic principle, which suggests a universe fine-tuned for life, and Stephen Hawking's Copernican jibe that humanity is "just a chemical scum on a moderate-sized planet". No wider gap of interpretation is imaginable.
Schrödinger's 1944 book opened with the conviction that physics and chemistry will one day account for what happens inside an organism, even if they could not yet. Pross notes that this promise is still unpaid despite a long run of Nobel prizes in molecular biology. Carl Woese, discoverer of the Archaea, went further, comparing biology in the early 2000s to physics before Einstein and Bohr: a field waiting for its revolution. Most biologists, Pross observes drily, carry on along the mechanistic path without noticing the alarm.
We know for certain there is no special life force; living things are built from the same "dead" molecules as rocks. Yet the way those molecules interact as a whole yields something unlike anything else. The paradox of modern biology is that we understand more and more of the cell's machinery while understanding no better what life is, how it relates to the inanimate world, or how it began.
The thought experiment
You walk through a field and find a working refrigerator with chilled beer inside, no cable in sight. A solar panel on top feeds a battery that drives the compressor, so the sun powers it and heat is pumped from cold to hot, against the normal direction of flow. How it works is solved. How it got there is not. Told that no one put it there, that natural forces assembled it, you would laugh: nature does not spontaneously build organized, far-from-equilibrium, purposeful objects.
The punchline is that a bacterial cell is exactly such an object, thermodynamically a refrigerator, but orders of magnitude more complex. A fridge has a few dozen parts; a bacterium coordinates thousands of molecular species in a network of thousands of synchronized reactions. Its function shows in what it does. Like a factory it is wired to an energy source, takes in raw materials, converts them into components and assembles an output. That output is more cells. François Jacob put it poetically: "the dream of every cell, to become two cells."
Why this is a real problem
If a fridge cannot assemble itself from a heap of parts, a self-building chemical factory seems even less likely. Common sense and the Second Law of Thermodynamics agree: systems drift toward disorder, not function. That is why Eugene Wigner, Niels Bohr and Schrödinger found biology troubling, and why Intelligent Design sells so well. Biology and physics look mutually incompatible.
Pross draws a methodological conclusion that runs through the whole book. The origin of life is not antiquarian family-tree research. Until the emergence paradox is solved we will not understand what life is, and the final proof of understanding will be a coherent recipe for synthesizing a chemical system we would call living.
Pross treats three questions as one: what life is, how it emerged, and how to make it. Answering any of them properly means answering all three.
The promise of the book
The bridge, Pross claims, is a young field that Günter von Kiedrowski named Systems Chemistry. Through it the gulf between chemistry and biology can be crossed, and Darwinism turns out to be the biological expression of a broader physicochemical principle. The key is a form of stability previously overlooked, which Pross calls dynamic kinetic stability (DKS). Folding DKS into Darwinian thinking gives a general (extended) theory of evolution covering both prebiotic and biological systems.
He enlists Darwin himself: in an 1882 letter to George Wallich, Darwin guessed that "the principle of continuity" made it probable that the principle of life would prove to be part or consequence of some general law. Pross sets out to show that Darwin was right and that chemistry, the science between physics and biology, can now sketch that law, while admitting the answers are still partly incomplete.
- Erwin Schrödinger: physicist; his 1944 What is Life? gives the book its title and its challenge.
- Carl Woese: microbiologist, discoverer of the Archaea; called for a revolution in biology.
- François Jacob: Nobel biologist; "the dream of every cell, to become two cells."
- Günter von Kiedrowski: chemist; coined "Systems Chemistry," the field Pross builds on.
- Charles Darwin: predicted in 1882 that life would prove part of a general law.
Living Things are so Very Strange
Before explaining life we must list what needs explaining. Pross sets out six properties that separate living from non-living matter: organized complexity, purposeful behaviour (teleonomy), constant turnover of parts, a special kind of diversity, a far-from-equilibrium energetic state, and homochirality. Each looks either strange or flatly at odds with the Second Law, and none has yet been explained in chemical terms, which is why both biologists and physicists still find life baffling.
The scale of the puzzle
Design is the oldest sign of life's oddity. The eye is the textbook case, but molecular biology has found design far deeper. The ribosome, present in thousands of copies in every cell, stitches a hundred or more amino acids into a protein in the right order within a few seconds, inside a structure only 20-30 nanometres across. Ada Yonath (Weizmann Institute), Venkatraman Ramakrishnan (LMB Cambridge) and Thomas Steitz (Yale) shared the 2009 Nobel Prize in Chemistry for solving it.
Diversity is equally striking: millions of species before we even reach the bacterial kingdom. And some properties are so obvious a toddler sees them. Pross's 2-year-old granddaughter happily played with toy dogs but feared real ones, because a real dog "had a mind of its own". Other properties are only visible in the laboratory, and some of them seem to violate basic physics, which is what troubled Bohr, Schrödinger and Wigner.
Biologists are hardly more comfortable. Carl Woese's recent description of organisms as "resilient patterns in a turbulent flow, patterns in an energy flow" strikes Pross as close to mystical, and telling: when one of the century's leading molecular biologists talks like that, the 3,000-year-old "what is life" riddle is plainly still open.
Pross works through six properties in turn: organized complexity, teleonomy, dynamic turnover, diversity, the far-from-equilibrium state and chirality.
1. Organized complexity
Richard Dawkins opens The Blind Watchmaker by calling animals the most complicated things in the universe. "Complexity" itself resists definition, and attempts to quantify it have not worked well in biology, so Pross focuses on what matters: organization.
A boulder is complex too, and describing its shape takes plenty of information, but its irregularity is arbitrary: any of a zillion other shapes would still be a boulder. Living complexity is specific. A single change among the 3 billion units of human DNA can cause disease (sickle cell anaemia, cystic fibrosis, Huntington's), and enough small changes stop a system living at all.
This organization reaches down to a bacterium a thousandth of a millimetre across: a nano-factory with molecular-sized parts that extracts energy, stores it in several chemical forms, synthesizes its building blocks and regulates itself, using pumps, rotors, motors, propellers and molecular scissors. The cell is a master chemist and a master physicist at once.
MAINTENANCE IS EASY, ORIGIN IS HARD
The Second Law in its simplest form says organized systems drift toward disorder. Shuffle a deck sorted as four aces, four kings, four queens and so on, and you almost always get a random order; Pross's desk proves the same law daily. Yet cells hold their organized state precisely, a phenomenon biology calls homeostasis ("standing still").
Maintenance is not a paradox. A cell stays organized by continually using energy, which is why we must eat. A car climbing a hill and a refrigerator keeping cool do the same against gravity and heat flow; plants use sunlight captured by chlorophyll. The energy books balance.
Origin is the hard part. Contrary to popular belief, Darwinian theory does not explain the emergence of the first cell. It explains how a primordial single cell, a "microbial Adam", became an elephant or a human. It is silent on how a system capable of evolving came to exist. That is a chemical problem, and Pross argues that applying biological concepts to it is partly why the field has stalled. Darwin himself judged the question premature and left it alone. Pure chance is out: Fred Hoyle's image of a whirlwind assembling a Boeing 747 in a junkyard (an analogy Pross notes was "famously misapplied") conveys the odds.
2. Life's purposeful character
Biologists call life's evident purposefulness teleonomy, a word coined about half a century ago to separate it from teleology and its cosmic overtones. As a pattern of behaviour it is empirically undeniable: every living thing builds nests, gathers food, protects its young and reproduces, and we predict the living world by reading agendas. Do not step between a mother bear and her cub.
In the inanimate world prediction works quite differently. Where a thrown ball lands follows from Newton's laws, not its purpose. Whether chemicals react follows from chemical rules. Purpose was expelled from physics in the seventeenth-century scientific revolution.
The inanimate world Governed by physics and chemistry. We exploit its laws: climb slopes, make fire and tools, fix leaking roofs. Technology is the art of using these laws. A physicist predicts it.
The teleonomic world Governed in practice by agendas. We cooperate (ordering a cappuccino) and compete (haggling, fending off intruders) with other purposeful beings. A biologist, psychologist, economist or lawyer predicts it.
The strangeness becomes clear with a fable: if all matter on Mars obeyed one set of principles and all matter on Venus another, we would be astonished. On Earth two classes of matter governed by different organizing principles sit side by side and constantly swap atoms, non-living becoming living and back again.
Pross is clear that physics still applies: a man falling off a ladder obeys gravity like a bag of sugar. But in the living world physical laws have little predictive value, as if "taken hostage" by a more dominant set of principles. No physicist can predict a crouching lion. A university shows the split: humanities, commerce and law study the teleonomic world, only the natural sciences study the physical one, and even there biology squirms between the two.
THE SKEPTIC IN THE CAR
Many biologists still recoil at "purpose", even repackaged as teleonomy, after the revolution overthrew 2,000 years of teleological thinking. Pross's reply: they stake their lives on teleonomy every time they drive. Each oncoming lump of metal could kill you; you accept the risk because every other driver shares your purpose of arriving in one piece. No one gets through a day without applying the teleonomic principle.
PURPOSE WITHOUT A BRAIN
Purpose is not a by-product of a nervous system. Put a bacterium in a glucose gradient and it swims toward the sugar: chemotaxis. E. Coli steers with several flagella: rotate them one way and it moves toward food; reverse them and it tumbles, changing course away from toxins. A membrane bag of chemicals with no neurons "goes out for dinner" like the lion. More deeply, nearly every component of the cell maps to a function, as the parts of a clock do, but at vastly greater intricacy; the Nobel run that began with Watson and Crick's 1953 DNA structure catalogues that design.
This raises the real question. A sugar crystal the size of a bacterium is inert; the bacterium acts for itself. Mixing a thousand organic chemicals in any combination does not make a living thing. Pross refuses the easy exit of "emergent properties of complex systems", which he calls the discredited life-force idea in respectable clothing. Jacques Monod was confounded by the same paradox (chapter 2). If life is material, teleonomy must be a property of the material, as hardness is of salt and bounce of rubber. We won't understand life till we understand teleonomy, and Pross promises a physicochemical account of it, with a mechanism for its emergence, in chapter 8.
WHAT IS THE PURPOSE?
Ask people their goals and you get a list without end: travel, money, the Olympic team, ten children, a book on life. Strip away multicellular complexity and look at the prokaryotic bacterium and the answer is single: everything it is and does serves cell division. In multicellular life, too, most goals are directly or indirectly means to reproduction.
IS TELEONOMY REAL?
Critics say teleonomy is only a concept in our heads. Pross agrees, and points out that gravity is too. Nobody has seen, heard or touched a gravitational field; it is a construct that organizes falling apples. All inferred patterns, the products of inductive reasoning (chapter 3), live only in minds. Gravity is quantifiable and teleonomy is not, and science rightly prefers quantifiable concepts, but unquantifiable does not mean unreal.
3. Life's dynamic character
The machine metaphor works: a cell, like a clock, has parts that each serve the whole, and the metaphor has guided research. But a clock's parts stay put until they wear out. A cell's parts are continually replaced.
You meet your friend Bill after a few years and tell him he hasn't changed a bit. Materially he is a different person: almost every molecule in him has been replaced. Hair and nails show the turnover openly; the rest happens unseen.
The human body has about 10,000 billion (10¹³) cells, plus 100,000 billion (10¹⁴) bacteria whose significance comes later in the book. Proteins, the archetypal molecules of life (muscle, cartilage, enzymes), must be policed for damage because faulty proteins can kill a cell. Avram Hershko and Aaron Ciechanover (Technion) and Irwin Rose (UC Irvine) won the 2004 Nobel Prize in Chemistry for showing that cellular protein is constantly degraded and resynthesized in a regulated process. Pross says much of our protein is remade within a few hours. Cells turn over too: billions of blood cells daily, constant skin renewal, and hundreds of billions of new cells a day in an adult, matched by deaths, many by programmed cell death. Over weeks you are materially someone else. Any answer to "what is life?" must explain this ephemeral, dynamic nature, which the machine analogy hides.
The 10:1 bacteria-to-human-cell ratio Pross repeats was revised in 2016 by Sender, Fuchs and Milo: about 3 × 10¹³ human cells and 3.8 × 10¹³ bacteria, roughly 1:1. Turnover is real but uneven: a 2021 estimate puts replacement at about 330 billion cells a day, mostly blood and gut cells, and typical protein half-lives in mammalian cells run to a day or two, while some molecules (lens crystallins, much neuronal DNA, tooth enamel) last a lifetime. "Almost every molecule replaced" is a useful exaggeration, not a fact.
4. Life's diversity
Non-living diversity is arbitrary; living diversity looks coherent, each of millions of species fitted to its niche. The microbial world is where diversity takes on new meaning:
The book's microbial figures:
- 2 × 10¹⁴ tons: an early estimate of Earth's bacterial biomass, enough to cover the land 1.5 metres deep.
- One billion: bacteria in a single litre of sea water.
- About a million: bacterial species in a gram of soil, by some estimates.
- 10 million to one billion: common range for bacterial species on Earth.
Genomes are so variable that microbiologists now think in pangenomes, a shared core plus a vast accessory set.
Yet the cause of diversity has troubled biology since Darwin. The Origin of Species proposed a Principle of Divergence, and Darwin never settled whether it followed from natural selection or stood alone. Pross sees a straight contradiction: divergence makes many from few, selection reduces many to few, "and no amount of verbal gymnastics can get around that". Variation in reproduction is clearly the start, but how it yields speciation remains disputed. Chapter 8 will offer a physical account of diversity and of the cooperation that accompanies it.
Most evolutionary biologists would not accept that divergence and selection are "inherently contradictory". Selection culls variants within a niche; divergence arises because different niches select different variants, so selection in a varied environment drives branching (as in adaptive radiation and ecological speciation models). The tension Pross describes is real in Darwin's own text, less so in modern theory. Biomass figures have also moved: Bar-On, Phillips and Milo (2018) put bacteria at about 70 gigatonnes of carbon, far below the old estimate.
5. Life's far-from-equilibrium state
A hovering bird stays aloft only while it flaps; stop and it falls. That is a metaphor for all life. A bacterium is thermodynamically unstable, in a far-from-equilibrium state that it maintains only by spending energy.
Pross's example is the ion gradient. Dissolve NaCl in water and it splits into Na⁺ and Cl⁻; local concentration differences soon vanish by diffusion, the Second Law at work. Cells, however, keep ion concentration gradients between inside and outside, essential for physiology. They do it with ion pumps driven by supplied energy, the cellular equivalent of flapping.
So maintenance again poses no mystery. Origin does. Prebiotic chemistry should have run downhill toward low-energy equilibrium, yet it produced complex, high-energy systems. In Second Law terms, "you can't get there from here". But we did.
6. Life's chiral nature
A molecule is chiral if its mirror image cannot be superimposed on it, like left and right hands (the book's Fig. 1). Biology still uses the old D/L classification (dextro/levo), defined by spatial relationship to glyceraldehyde. Mirror forms have essentially identical physical and chemical properties, so an arbitrary environment should contain equal amounts. Start with pure D and the Second Law says it will slowly become racemic (50:50) through D⇄L interconversion, because the racemic mix is more disordered and so more stable.
Life is homochiral: sugars almost always D, amino acids almost always L. Two questions follow:
- Origin. How did a heterochiral world become single-handed in its biological part?
- Maintenance. Given that racemic mixtures are more stable, how is homochirality kept? Homochirality is another instance of life's unstable, far-from-equilibrium character.
Several routes to symmetry breaking now have experimental support: Soai autocatalysis and Viedma ripening (both earlier), Blackmond's work on amplification, and in 2023 Ozturk and Sasselov's report that magnetite surfaces can select one handedness of an RNA precursor via spin-polarized electrons. Samples returned from asteroid Bennu (analysed 2025) carry amino acids in near-racemic mixtures, consistent with life making, not inheriting, its handedness. No route is yet agreed.
Why water is understood and life is not
Living and non-living things differ, but that alone is no problem: matter comes in many forms. Ice, water and steam could hardly be more different, yet we understand them. Kinetic-molecular theory explains each state from the strength of intermolecular forces against the kinetic energy set by temperature. And we can control them: phase diagrams tell us to melt ice by heat or by pressure, or to turn ice to steam without passing through liquid.
Pross's test of understanding has two parts: (a) explain the properties in fundamental molecular terms, and (b) gain control, the ability to convert one state into another. For life we pass neither test.
The biological class of matter shows a distinct behaviour pattern unexplained in chemical terms, even as the cell's mechanisms become ever better known. We see more and more trees and still no forest. Offering clear explanations for the six strange properties is the book's challenge.
| Property | What we observe | Why it is strange |
|---|---|---|
| Organized complexity | Specific, fragile organization | Chance assembly impossibly unlikely |
| Teleonomy | Agenda-driven behaviour, even in bacteria | Matter is supposed to lack purpose |
| Dynamic character | Constant molecular and cellular turnover | Machines keep their parts |
| Diversity | Millions of adapted species | Selection should narrow, not widen |
| Far from equilibrium | Gradients held by pumps | Prebiotic chemistry runs downhill |
| Homochirality | L-amino acids, D-sugars | Racemic mixtures are more stable |
The Quest for a Theory of Life
Each great revolution in thought made the life problem harder, not easier. Aristotle gave the cosmos a single purposeful logic; the scientific revolution removed purpose from nature and so split the world in two; Darwin explained biological design mechanically but not life's origin; twentieth-century physicists and molecular biologists then deepened the mystery. Attempts to define life have multiplied without converging, and Pross sides with Cleland and Chyba: what we need is not a definition but a theory of life.
Aristotle's unified, purposeful world
Aristotle was a working biologist, and his close study of living things produced what Pross calls his most important idea: a teleological view of nature. Reproduction and embryonic development are plainly goal-directed. Since purpose showed up in so many material forms (all of them, in fact, biological), it seemed logical to assume purpose governs all matter: the famous Final Cause. With so much biological evidence behind it, teleology went essentially unchallenged for over two millennia.
The scientific revolution splits the world
From the sixteenth century a stirring grew into an intellectual tsunami. Copernicus, Descartes, Galileo, Newton and Bacon replaced cosmic purpose with the axiom that nature is objective, with no underlying purpose. Jacques Monod rated this the single most important idea humans produced in their 150,000-200,000 years on the planet.
The irony is that the revolution sharpened the life riddle. Before it, teleology gave a kind of unity: animate and inanimate shared one logic. After it, science had to explain two worlds and the relationship between them. The revolution was slow to win precisely because Aristotle's case rested on such abundant, empirical, biological evidence of design.
Darwin closes one gap and opens another
Darwin's On the Origin of Species (1859) knocked away teleology's strongest support by showing that a mechanistic process, natural selection, produces purposeful design. That carried the scientific revolution into the one domain where it had seemed not to apply, and cosmic teleology was finally laid to rest in science.
But Darwin explained how simple life became complex life, never how matter became life. He knew it: "it is mere rubbish thinking at present of the origin of life; one might as well think of the origin of matter." Ernst Haeckel was less gentle, calling the missing origin "the chief defect" of the theory and suggesting Darwin, in assuming a special creative act for the first species, was "not quite sincere". So, paradoxically, Darwin's grand unification of biology widened the chasm between living and non-living.
The physicists give up
- Niels Bohr, 1933. In his "Light and Life" lecture Bohr proposed that life is consistent with, but undecidable from, physics and chemistry, extending quantum theory's accepted "irrationality" into biology.
- Erwin Schrödinger, 1944. Puzzled above all by life's thermodynamic behaviour, he concluded that living matter, while obeying known physics, probably involves "other laws of physics" not yet discovered.
- Jacques Monod, 1971. In Chance and Necessity Monod located the central problem of biology in teleonomy, which seems to violate the founding principle of science, the objectivity of nature.
"Here therefore, at least in appearance, lies a profound epistemological contradiction." Jacques Monod, Chance and Necessity
Monod's contradiction is the book's target. How could function and purpose emerge in a universe without them? Pross draws two consequences. Understanding life requires understanding teleonomy; and, more hopefully, a physical account of teleonomy might reveal the mechanism by which life emerged. Chapters 7 and 8 argue for that link.
Molecular biology deepens the mystery
One might think physicists failed because the problem is chemical, and that knowing the chemistry would settle it. The half-century after Watson and Crick's 1953 DNA paper says otherwise. DNA replication, protein synthesis, energy transduction and the central metabolic cycles were worked out in quick succession, yet none of it answered Schrödinger.
- Karl Popper, 1974. Two decades after DNA, Popper called the origin of life "an impenetrable barrier to science" and a residue resisting all attempts to reduce biology to chemistry and physics.
- Francis Crick, 1981. In Life Itself Crick found life's emergence so nearly miraculous that he entertained directed panspermia, the seeding of Earth by an alien civilization.
What molecular biology has delivered is detailed confirmation of Darwin: all life is cell-based, information is stored in DNA, proteins are made through a universal genetic code, and energy is stored in ATP. These facts confirm that life is one thing, descended from a common ancestor. Sixty years of extraordinary molecular discoveries have not brought us closer to answering what life is; we see many trees, but the forest stays obscure.
The definition game
Hundreds of definitions of life exist and the flow is not slowing. Radu Popa's Searching for the Definition and Origin of Life lists forty proposed in 2002 alone, which Pross jokes shows the activity has an autocatalytic streak. Four from Popa's list barely overlap:
| Proposer | "Life is…" | Focus |
|---|---|---|
| Freeman Dyson | A system that acquires, stores, processes and uses information | Software |
| Victor Kunin | Nucleic acid and protein polymerases with monomers, energy, protection | Hardware plus energy |
| Gustaf Arrhenius | Self-organization, self-replication, mutation-driven evolution, metabolism, concentrative encapsulation | Checklist of traits |
| Remy Hennet | A particular state of organized instability | Thermodynamics |
Strip off the opening "Life is…" and you would think they described different things. Life is indeed many things, yet none alone is life.
THE NASA DEFINITION AND ITS MULES
The most widely accepted version, from the NASA Exobiology Program (Pross dates it 1992), reads: life is a self-sustained chemical system capable of undergoing Darwinian evolution. Pross raises two objections:
- The technical flaw. Individuals cannot evolve; they only reproduce and die. Only populations evolve, so the definition does not fit a single bacterium or elephant.
- The exceptions. A mule is sterile, so a population of mules cannot evolve; neither can a solitary rabbit. Both are alive. The objection is old and familiar, Pross admits, but familiarity does not weaken it. Definitions either exclude living things or let non-living things in.
CLELAND AND CHYBA: CART BEFORE HORSE
Carol Cleland (philosopher, University of Colorado) and Christopher Chyba (astronomer, Princeton) reframed the debate about a decade before the book: defining something before we understand it is futile. The NASA definition does not say what life is; it says how to recognize it, the way physical properties tell you whether a liquid is water. What is needed is a comprehensive theory of life, which Pross attempts in his final two chapters.
A definition of life is a field guide, not an explanation. Until physics and biology merge, Pross says, the nature of life and our place in the universe stay "gnawingly uncertain".
The NASA working definition is usually credited to Gerald Joyce and an Exobiology Program panel, and most sources cite its wording from 1994. In chapter 1 Pross credits Monod's Nobel to DNA replication; the 1965 prize (with Jacob and Lwoff) was for the genetic control of enzyme and virus synthesis. The definition debate itself has continued: Cleland's own book The Quest for a Universal Theory of Life (2019) presses the theory-not-definition line, and Trifonov's 2011 word-frequency analysis of 123 definitions distilled them to "self-reproduction with variations".
Understanding 'Understanding'
Before claiming to understand life, Pross asks what scientific understanding is. His answer: induction, the recognition of patterns, and nothing deeper. Every law is a pattern that places the particular inside the general, so understanding comes in degrees and can take several valid forms. He then argues that the long quarrel between reductionism and holism is mostly semantic: holism is reduction with feedback added, and life will be understood only by reducing the living/non-living difference to chemistry.
Understanding is pattern recognition
The scientific method rests on induction, reasoning from observed facts to general conclusions, with roots in Greek philosophy and its formal statement by Francis Bacon. Pross's bold claim: stripped of jargon, all science is the successful application of the inductive method, and that success is what we call "understanding".
The method is simple enough for a toddler. All apples fall, so "apples fall"; all objects fall, so "objects fall", with refinements for exceptions like hot-air balloons. Thomas Macaulay noted over 150 years ago that induction is practised by "the most ignorant clown" who expects barley not wheat from barley seed, by the schoolboy who learns cloudy days are best for trout, and by the infant who expects milk from its mother and none from its father. Your dog does it when the can opener comes out. Evolution built pattern recognition into every cognitive being because it lets them respond to the world to their own benefit; child, dog and scientist differ only in how sophisticated the patterns are.
THE LADDER OF GENERALITY
Newton saw that falling apples and the orbiting moon belong to one pattern, universal gravitation, expressed mathematically. Einstein's relativity then placed Newton's force inside a broader pattern: gravity as motion through curved four-dimensional spacetime. String theory and M-theory chase the ultimate pattern, a theory of everything, whether or not one exists.
The catch is that there is no deeper "why". Gravity is just the name of the pattern to which falling apples belong. All scientific explanation is inductive: it associates the specific with the general, and the wider the generalization, the greater its predictive power.
NUMBERS HELP BUT ARE NOT REQUIRED
Mathematics magnifies a pattern's predictive reach. Richard Feynman likened the precision of quantum theory to measuring the width of North America to one hair's breadth. But qualitative patterns count too: Darwin's natural selection and common descent were entirely qualitative yet reshaped how humanity sees itself. Pross quotes the aphorism attributed to Einstein: not everything that counts can be counted.
WHY "PATTERN" BEATS "LAW"
Scientists say hypothesis, theory, law, the difference being how well confirmed the pattern is. Pross prefers "pattern" because it is fuzzier and less committed. Newton's laws had to be revised after Einstein; if every law is understood as a pattern, its revision is less shocking.
"The whole modern conception of the world is founded on the illusion that the so-called laws of nature are the explanations of natural phenomena." Ludwig Wittgenstein, Tractatus
For Pross the pattern is the explanation. Patterns link reality to our grasp of it; why the patterns exist is philosophy, and here he follows Wittgenstein's other line: "whereof one cannot speak, thereof one must be silent".
Understanding comes in degrees
Because pattern recognition is partly in the eye of the beholder, understanding is partly subjective. Steven Weinberg offered a practical test: a good pattern makes colleagues say "Aha!"
- Physics. Patterns are quantified; exceptions are not tolerated and force reformulation.
- Biology. Patterns are often qualitative; exceptions are normal.
- History and social science. Patterns are statistical, so the same facts support rival models, as the literature on the causes of the First World War shows.
Patterns need not exclude each other. The child's "objects fall" and the physicist's general relativity both explain apples; the child's version is all that matters unless you are launching satellites, and a physicist climbing a mountain relies on "objects fall", not string theory. Which pattern is best depends on use: Pross borrows Woody Allen's 2009 film title, Whatever Works. No pattern fully captures reality; patterns are reflections of it, some better than others.
Understanding is placing a phenomenon inside a wider pattern. That reframes the life problem: to understand life is to find the chemical pattern of which biology is a special case. That is the program of chapters 7 and 8.
Reduction or holism
Reduction is the most productive kind of induction: the whole is understood through the interactions of its parts, as a clock is understood through its wheels, cogs and springs. Holism answers that the whole is more than the sum of its parts: complex systems show emergent properties absent at lower levels. Holism's rise in biology, driven by the complexity of even "simple" cells, produced systems biology; Carl Woese recast organisms as "complex dynamic organization" rather than molecular machines.
- Jacques Monod: dismissed the quarrel as "foolish and wrongheaded", showing the holists' "profound misappreciation" of analysis.
- June Goodfield: at the September 1972 Bellagio meeting "Problems of Reduction in Biology" (with Medawar, Monod, Popper), confessed déjà vu "verging on intellectual impotence".
- Denis Noble: recent polemic firmly for holism, drawing on systems biology.
- Carl Woese: "reborn holist"; the molecular paradigm "has run its course" and risks turning biology into engineering.
- Sydney Brenner: deducing function from a complex system's behaviour is an inverse problem "impossible to solve".
- Steven Weinberg: "explanatory arrows always point downward".
Nearly forty years after Bellagio, nothing is clearer. Pross enters the "philosophic lion's den" with a thesis: the divide is more semantic than substantive, and holism is a more elaborate reduction.
HIERARCHICAL REDUCTION
The useful form is hierarchical reduction: explain each level using concepts from the level just below. Social behaviour from organisms, organisms from cells, cells from biochemical cycles, cycles from molecular structure and reactivity, down to subatomic particles. This method drove physical science since the seventeenth century, and in biology yielded DNA replication, protein synthesis and metabolic cycles: molecular biology is "reduction par excellence".
EMERGENCE IS OFTEN REDUCIBLE
Critics attack extreme reductionism, such as Francis Crick's aim "to explain all biology in terms of physics and chemistry". Pross agrees that is unrealistic for now, an "ultimate aim" in the same sense as predicting all of chemistry by solving Schrödinger's wave equation. But the claim that reduction cannot handle emergence is simply wrong.
Condensed states prove it. Solidity, liquidity, conductivity and shine are absent in a single molecule, yet we explain why hydrogen is a gas, water a liquid and table salt a solid at room temperature from molecular weight, charge character and intermolecular forces. Solid-state conductivity can be predicted by analysing an isolated molecule. Physics and chemistry are full of such reductive explanations of emergent properties, though not every emergent property yields.
Reduction Dissects the system into parts and explains the whole by their interactions. Upward causation. Enormously productive; strained by biological complexity.
Holism (systems approach) Also dissects into parts, but models their interactions more realistically, including downward causation and feedback that yield surprising emergent behaviour. In practice, an elaborate reduction.
Athel Cornish-Bowden catches the shift: classical reduction explains wholes by parts, but "now we must learn to understand the parts in terms of the whole". Decades of hoping for a non-reductionist method have "not yet borne edible fruit". Reduction was, is and will remain the central tool of science, and if the "what is life" question can be solved at all, it will be by reducing the difference between animate and inanimate to differences in how their materials interact and react.
Pross's "induction is all of science" skips Popper's falsificationism and the role of hypothetico-deductive testing, and his claim that holism is just reduction would be disputed by Noble and by philosophers of downward causation who see a real explanatory difference. Minor point: the "not everything that counts can be counted" line, popularly pinned on Einstein, traces to sociologist William Bruce Cameron (1963).
Stability and Instability
This is the chemical engine room of the book. Ordinary reactions run downhill toward thermodynamic stability, gated by kinetic barriers. But self-replicating molecules are autocatalytic, so they grow exponentially, and a population of them can only persist as a molecular fountain, constantly made and unmade. That persistence is a second kind of stability, dynamic kinetic stability (DKS), with its own selection rule: replicators are transformed from less to more kinetically stable forms. Spiegelman's RNA experiment shows the rule at work, and it nests inside the Second Law like a Russian doll.
Why chemical reactions happen
A living cell is thousands of reactions coordinated into one whole, so understanding life starts with understanding chemical reactions in general. Pross offers a deliberately simplified account, keeping only what his later argument needs, and promises that something very special lurks inside the set of reactions that make up life.
A reaction turns one material into another: acid neutralized by base, protein broken into amino acids, hydrogen and oxygen exploding into water. That last one needs only a spark or a platinum or palladium catalyst. The reverse, water splitting spontaneously into gases, never happens. The Second Law of Thermodynamics sets the direction: reactions turn less stable materials into more stable ones, like a ball rolling downhill. "Downhill" means toward lower free energy. Water has lower free energy than H₂ + O₂, so the gases react and the stored energy is released as heat.
The book's free-energy diagram adds a second point. Between reactants and product sits a barrier: the path climbs before it falls. A spark supplies the boost to get over it; a catalyst lowers the barrier so no boost is needed.
- Thermodynamics sets the direction. A reaction happens only if products have lower free energy than reactants. At the lowest reachable state the mixture is at equilibrium and stops reacting, like balls in a valley.
- Kinetics sets the pace. A mixture not at equilibrium may still not react if it is trapped behind a barrier in a local minimum, like a ball in a hollow halfway down a slope. Hence H₂ and O₂ can sit mixed indefinitely.
- The rule. A thermodynamically allowed reaction may or may not proceed; a thermodynamically forbidden one cannot.
ENTROPY
Entropy is, intuitively, disorder. Throw building blocks on a table and they land in a heap, not a stack; the Second Law can be phrased wholly in terms of entropy, and explained statistically. Chemical systems drift toward disorder for the same reasons tidy desks do. So, energy aside, combining two molecules into one is entropically unfavourable (order rises), while breaking one molecule into fragments is favoured (order falls). Free energy includes this entropic contribution.
Catalysis versus autocatalysis
Almost any reaction can be catalysed by something, and in biology catalysts are enzymes, without which most biological reactions would crawl or stop. Usually catalyst and product differ. In an autocatalytic reaction the product is the catalyst: it speeds its own formation.
The difference sounds minor and is enormous. Start each with a single molecule of catalyst and ask how long it takes to make 100 grams of product. Ordinary catalysis: billions of years. Autocatalysis: a tiny fraction of a second. Pross jumps ahead to announce that the essence of life will be found in this difference between catalytic and autocatalytic rates.
The reason is exponential versus linear growth. Pross tells the legend of the Chinese emperor rescued by a peasant who asks for rice on a chessboard: one grain on the first square, two on the second, four on the third, doubling to the 64th. The total is 2⁶⁴ − 1, about 2 × 10¹⁹ grains, more rice than exists on Earth, enough to cover the planet several centimetres deep. Linear growth, one grain per square, gives 64 grains.
Autocatalysis is common. Acetone plus bromine gives bromoacetone and hydrogen bromide; the reaction is acid-catalysed and HBr is an acid, so it speeds up as it goes. But Pross's interest is a different and far more significant class, discovered about forty years before the book: molecules that copy themselves.
Molecular self-replication
In 1967 Sol Spiegelman (University of Illinois) ran one of molecular biology's classic experiments: replication in a test tube. He mixed an RNA strand with its free building blocks and an enzyme, and the RNA made copies of itself.
RNA is a chain of nucleotides of four kinds, U, A, G, C, so a strand is a sequence such as UCUUGAGCC. The number of possible sequences explodes with length: for 100 nucleotides it is 4¹⁰⁰ ≈ 1.6 × 10⁶⁰. The strand finds the one right sequence by acting as a template:
- Lock-and-key pairing. Free nucleotides latch onto the template by complementarity: U to A, A to U, C to G, G to C.
- Linking. Held side by side, the aligned nucleotides join into a new chain, giving a double strand held by weak hydrogen bonds.
- Separation. The weak bonds let the strands part: two molecules where there was one.
- Two cycles for a true copy. The new strand is a negative, like a photographic negative; copying the negative gives back the positive.
Without a template, free nucleotides do not readily link up, and certainly not in a set order. Self-replication is by definition autocatalytic, so like the rice it can amplify minute amounts exponentially, provided building blocks last.
Cells replicate DNA at every division, but inside a highly regulated, organized environment. Replication in isolation was unknown to chemistry until 1986, when Günter von Kiedrowski achieved the first enzyme-free molecular replication, "pure replicative chemistry". Spiegelman's system had needed an enzyme.
Pross's three chemical points: (1) reactions run only downhill thermodynamically; (2) allowed reactions may stall behind kinetic barriers; (3) template self-replication is a real reaction and kinetically unique, able to amplify exponentially until building blocks run out. A replicating molecule is not life, but its kinetic power leads to a distinct branch of chemistry, so distinct it goes by another name: biology.
Two kinds of stability
Stability means persistence: staying unchanged over time. It comes in two forms:
- Static stability. Isolated water stays water. Thermodynamic stability is static: stable things are those that do not react.
- Dynamic stability. The River Thames, once a tributary of the Rhine (some 30 million years ago), has kept its present course for thousands of years, yet its water is never the same. A fountain or waterfall persists while its water is constantly replaced.
Replication forces populations into the second kind. Exponential growth is unsustainable: a single molecule replicating 160 times would in principle consume the mass of the Earth. So any replicating population that persists must have its rate of formation roughly balanced by its rate of decay. Decay is never far off: RNA oligomers and peptides, the prime replicating molecules, are thermodynamically fragile; living replicators die of starvation, attack, damage or apoptosis. What is stable in a replicating system is the population, not the individuals, which turn over like droplets in a fountain; a stable population of replicating molecules is a molecular fountain. Life's dynamic character, which puzzled biologists in chapter 1, follows directly.
DYNAMIC KINETIC STABILITY
Here the paradox appears. In ordinary chemistry stable means unreactive. In the replicator world a system persists only if it does react, making more of itself, and the more reactive (better replicating) systems are the more persistent. Greater stability goes with greater reactivity. Pross calls this dynamic kinetic stability: "dynamic" for the turnover, "kinetic" to separate it from the purely physical dynamic stability of rivers.
- High DKS. Fast replication and slow decay give a large population. Mosquitoes and cockroaches are, to our chagrin, highly stable in this sense.
- Low DKS. Pandas replicate slowly; low DKS risks extinction.
Which kind is more enduring? The two are apples and oranges, and DKS is only quantifiable in limited ways. But intuition misleads. Mount Everest, statically stable, is thought to be some 60 million years old. Cyanobacteria appear to have populated the Earth for 2.5-3.5 billion years with little morphological change, a dynamic stability spanning much of the planet's 4.6-billion-year history.
Regular chemistry Mature, studied for centuries. Stability is thermodynamic. Selection rule: the Second Law, transformations toward lower free energy.
Replicative (systems) chemistry Infant field, systematically studied for about 25 years; many chemists do not know it exists. Stability is dynamic kinetic. Selection rule: transformations toward greater DKS.
The selection rule of the replicator world
Richard Dawkins (1989) spoke of a general law, survival of the most stable; Steve Grand (Creation, 2001) put it as "things that persist, persist; things that don't, don't". Tautology, partly, but with a real message: once matter can change, it must drift from less persistent to more persistent forms. Kinetics and thermodynamics are the science of predicting that drift, and for ordinary matter the governing law is the Second Law.
For transformations of one replicator (or set) into another, the relevant stability is dynamic kinetic, so the governing rule is:
Replicating chemical systems will tend to be transformed from (dynamically) kinetically less stable to (dynamically) kinetically more stable. It is the replicator world's analogue of the Second Law: same drive toward stability, different kind of stability.
SPIEGELMAN'S MONSTER
The evidence is the part of Spiegelman's experiment Pross held back. Copying is occasionally wrong (a C instead of an A opposite a U), producing mutant strands. Over time, mutants that replicated faster took over and the original sequence could vanish entirely: molecular Darwinian selection. Because short strands copy faster, the RNA shrank from about 4,000 nucleotides to about 550. The runaway short replicator was dubbed Spiegelman's Monster.
The process is chemical, not biological: an RNA strand is "a molecule is a molecule is a molecule". When replicators compete for shared building blocks, faster ones out-replicate slower ones, exactly as the selection rule predicts.
THE RUSSIAN DOLLS
Does the replicator rule break the Second Law? No. No system escapes the Second Law; the DKS rule operates within its constraints, like a smaller Russian doll inside a larger one. Pross's analogy: your car breaks down and the mechanic blames the Second Law. He is right and useless. You want to know whether the fuel line blocked or the timing belt snapped, the rules of the engine doll. Saying evolution is "governed by the Second Law" is just as correct and just as unhelpful. In later chapters biological terms such as fitness will turn out to be chemical terms such as stability.
Since publication. Pross developed DKS with Robert Pascal (Open Biology 2013, with John Sutherland; formal treatments in 2014-15). Critics answer that DKS restates fitness for chemistry and, as Pross concedes, is hard to quantify. On details: Spiegelman's Qβ RNA started at roughly 4,200-4,500 nucleotides, and later variants of the "monster" shrank to about 220. Cyanobacterial antiquity is now debated; molecular clocks and oxygenation records put the group at roughly 2.5-3 billion years, not 3.5.
The Knotty Origin of Life Problem
Origin-of-life research has two faces: the historical "how" (which molecules, where, in what order) and the ahistorical "why" (what drives any matter toward life). Pross argues that every historical tool, fossils, phylogeny and prebiotic chemistry, has failed to reach abiogenesis, and that both rival schools, replication first and metabolism first, hit the same wall: a downhill chemical world should not build far-from-equilibrium systems. The tractable and more important question is the ahistorical one, and it can be studied in present-day laboratories through systems chemistry.
A frank admission
The question is as old as Genesis, but the modern debate starts in the early twentieth century. George Whitesides of Harvard summed up the state of play: most chemists believe life arose spontaneously from prebiotic molecules; "How? I have no idea." Pross's review is deliberately critical rather than comprehensive.
The working assumption, unproven, is that life began from abiotic matter some time after the solar system formed 4.6 billion years ago. That view took shape in the 1920s through Alexander Oparin (Russian biochemist) and J. B. S. Haldane (British geneticist). The alternative, panspermia, proposed by Svante Arrhenius in the early twentieth century and backed by figures like Francis Crick, is no longer taken seriously by most researchers. Its flaw: it only relocates abiogenesis to an unknown cosmic address. Wherever life began, the question stays: how did life come from non-life?
Historical and ahistorical questions
- The historical "how". Deciphering the actual chemical path on the prebiotic Earth: which building blocks, under what conditions, through which intermediates. There is no agreement on any of it, and almost no hard knowledge of prebiotic conditions.
- The ahistorical "why". Why would matter of any kind complexify in the biological direction? Pross wants the kind of driving force Newton found for falling apples: a general principle, independent of particular molecules, that would make life a matter of established physicochemical forces, not a pure fluke.
THE BOULDER
A boulder, dislodged by erosion or an earthquake, rolls downhill and stops. The historical question: where did it start and what path did it take? The ahistorical one: why did it roll? The answer, gravity lowering potential energy, is a general law independent of terrain. Each kind of knowledge informs the other. Knowing gravity rules out a boulder that levitated to its resting place. Conversely, mapping trajectories without knowing gravity would reveal that boulders always roll downhill, by steepest descent, and so expose the law.
For life, both kinds of knowledge are missing. Without the principles we do not know which history to look for; without the history we have no data to infer the principles. Catch-22.
Pross's controversial stance: the ahistorical question is both more significant and more tractable. Historical scenarios built without understanding the principles have failed, are often untestable, and being highly specific they do not answer the general question. They may even have added to the confusion.
The historical tools
FOSSILS
Earth formed about 4.6 billion years ago, and its first 600-800 million years were probably too hostile: heavy bombardment could boil off the oceans and sterilize the surface. The earliest microfossils date to about 3.4 billion years and already show fairly advanced cells. Indirect chemical evidence for life at 3.8 billion years is claimed but disputed. The morphological record runs out where cellular life is already established, so fossils say nothing about abiogenesis.
SEQUENCE ANALYSIS
Max Delbrück said in 1949 that every living cell carries "the experience of a billion years of experimentation". Phylogenetic (sequence) analysis reads that experience. Nucleic acids (4 nucleotides) and proteins (20 amino acids) vary in sequence; the closer two species are, the more similar the sequences of molecules they share. Compare enough species and you get a tree of life, with the Last Universal Common Ancestor (LUCA) at its root and extinct lines as truncated branches.
The method's triumph came in the late 1970s. Carl Woese's ribosomal RNA sequencing showed that archaea, prokaryotes of hot springs and salt lakes once lumped with bacteria, are closer to eukaryotes than to bacteria. The two-kingdom tree (Prokarya, Eukarya) became three: Archaea, Bacteria, Eukarya.
Then the trouble began. Whole-genome sequencing in the 1990s produced conflicting tree topologies depending on which molecules were compared: A close to B by one probe, close to C by another. The cause was Horizontal Gene Transfer (HGT), genes passing to organisms other than offspring, as against normal vertical transfer from parent to child. The deeper you go, the more HGT dominates. Woese himself argued that early cellular organization was loose, modular and communal, without stable genealogies. LUCA may be an artefact of forcing a tree onto the data. For archaea and bacteria the tree has become a web of life, and a web, unlike a tree, leads back to no root. Extrapolating to pre-LUCA entities is therefore doubtful.
Prebiotic chemistry: from superhighway to dead end
Oparin's 1924 paper "The Origin of Life" floated early ideas, but the field launched with Stanley Miller, a graduate student of Nobel chemist Harold Urey at Chicago. Miller passed electric sparks, standing in for lightning, through hydrogen, ammonia, methane and water vapour, the presumed early atmosphere, and got organic compounds including several amino acids. Within a few years the organic bases of nucleic acids were also made under plausible conditions. For a while the road to life "looked like a superhighway".
Then came dissent. Where did life start? The prebiotic soup gave way to rivals as different as deep-sea hydrothermal vents and clay surfaces. Was the atmosphere reducing, as Miller assumed, or neutral (CO₂, N₂, water)? Optimism turned to incoherence. The only point of agreement was that life emerged from inanimate matter about 4 billion years ago. The work uncovered new reactions, but Pross attacks its guiding thesis: that studying reactions under "prebiotic conditions" can trace the path to life.
- Unknown conditions. "Conditions on today's Earth" already means volcanoes, Arctic ice, deep vents, the Sahara or a lagoon. For the prebiotic Earth we know neither the place nor the conditions, and reaction mechanisms are sensitive to conditions. Scenarios are unfalsifiable; as Leslie Orgel joked, "just wait a few years and conditions on the primitive Earth will change again."
- Proving the negative. Failure to make something does not show it could not form. The anti-RNA-world argument (decades of failure to make nucleotides prebiotically) collapsed when John Sutherland made a pyrimidine nucleotide by a new route. Absence of evidence is not evidence of absence; nature may "think out of the box" too. Peter Schuster: "Never say never!"
- Building blocks are not a recipe. Even total success in making sugars, bases, nucleotides, amino acids and lipids would leave the riddle intact.
The third objection is the deepest. Give the best biochemists, synthetic chemists and molecular biologists unlimited materials, conditions and money, simulated vents, clays, whatever they want, and ask them to make something alive. Honestly, most would not know where to start. Jack Szostak (Harvard) and Pier Luigi Luisi have taken tentative steps, but the barrier is not one hard step. There is no coherent recipe, because we do not understand what life is.
So Pross calls the historical search a honey trap: seductive to novice and expert alike, unlikely to yield insight, and insufficient even if the history were known. The heart of the origin-of-life problem is the ahistorical question: what physicochemical process would turn inanimate matter of any kind into a system we would call living? Hunting for life's molecular beginnings first is like assembling a watch from springs and cogs without knowing how watches work. Feynman's "What I cannot create, I do not understand" should be turned around: what I do not understand, I cannot create.
The good news: ahistorical principles hold today as they did 4 billion years ago. Instead of speculating about the past, study chemical systems of the right kind now. Systems chemistry, the study of replicating molecules and their networks, already shows reactivity patterns unlike regular chemistry.
Replication first or metabolism first?
The longest-running debate in the field looks historical but may be settled by chemical logic, and it bears on all three corners of what Pross calls the triangle of holistic understanding: what life is, how it emerged, how to make it.
- Metabolism. The coordinated, mutually regulated network of reactions in every cell. Metabolism first proposes that a simple autocatalytic cycle preceded any genetic polymer. Stuart Kauffman showed in the 1980s that if A catalyses B, B catalyses C, C catalyses D, D catalyses E and E catalyses A, the closed cycle is autocatalytic as a whole: collectively self-replicating.
- Replication. Replication first proposes that a template oligomer such as RNA (or something RNA-like) appeared, then mutated and complexified into life.
Freeman Dyson first posed the question directly, proposing that a genetic system and a metabolic system arose independently and later merged. Pross finds this arbitrary: if either emerging spontaneously is doubtful, both doing so independently is less likely still. That two schools persist shows neither is compelling, and shows how rudimentary our understanding is.
THE RNA WORLD
Replication first goes back to physicist Leonard Troland in 1914, gained a big boost from Spiegelman in the late 1960s, and was developed in the 1970s by Manfred Eigen and Peter Schuster. Its centrepiece is the RNA world, which dissolves the chicken-and-egg problem of modern life: DNA cannot replicate without protein enzymes, and those enzymes cannot be made without DNA. If RNA was once both gene and enzyme, the circle breaks. RNA obviously carries information; the discovery by Thomas Cech (Colorado) and Sidney Altman (Yale) that RNA can also catalyse reactions (the ribozyme) won them a Nobel and boosted the hypothesis.
Pross rejects the usual objection, that prebiotic conditions forbade a self-replicator: replicators can be made in the lab, and ignorance of the early Earth cannot rule them out. His objection is thermodynamic. Simplest life is a highly organized far-from-equilibrium system that must consume energy. For a replicating molecule to complexify into it, chemistry would have to run uphill. A replicating reaction should run only until it reaches equilibrium and stop. Four decades of replicator experiments show no tendency to complexify toward metabolic systems.
METABOLISM FIRST
Whatever their chemistry, metabolism-first schemes share two premises: holistic autocatalysis (a closed catalytic cycle) came before genetics, and the organization of that cycle arose spontaneously or by random drift. Shneior Lifson and Leslie Orgel pointed out the problem: it is the Second Law again. How would organized cycles form from simple molecules, and how would they maintain themselves? Pross invokes Harry Truman: "I'm from Missouri, show me." No one has.
| Replication first | Metabolism first | |
|---|---|---|
| First entity | Template oligomer (RNA-like) | Closed autocatalytic cycle |
| Key names | Troland, Spiegelman, Eigen, Schuster, Cech, Altman | Kauffman, Dyson (dual origin) |
| Strength | Solves gene/enzyme chicken-and-egg | No need for a complex polymer |
| Standard objection | Prebiotic nucleotides impossible (rejected by Pross) | Spontaneous organization unlikely |
| Pross's objection | Replicators should not climb uphill | Organized cycles should not self-assemble |
Both schools fail for the same deep reason: neither explains how a downhill chemical world produces and sustains far-from-equilibrium organization. Solve that, and "which came first?" may answer itself or stop mattering. Pross offers his solution in chapter 7.
Chance or necessity?
Was life a near-impossible fluke or an inevitable outcome of physical law? Jacques Monod: its prior probability was "virtually zero"; "the universe was not pregnant with life nor the biosphere with man." Christian de Duve called life a cosmic imperative: "It is self-evident that the universe was pregnant with life and the biosphere with man. Otherwise, we would not be here."
Pross reframes these as two ends of a spectrum, using winter snow. In the Swiss Alps it is effectively certain; on a Queensland beach, essentially impossible; in Rome, contingent: it snowed in 2012, 2005 and 1986, about a 10 per cent chance in a given winter. You do not need meteorology to know this; the historical record is enough.
For life we have neither. We do not understand the process or the conditions, so we cannot compute the odds, and the historical record is a sample of one: among a likely vast number of Earth-like planets, we know life on just ours. On chance versus necessity we can say, for now, almost nothing.
- Earliest life. Contested signs now reach 3.7 billion years (Greenland, 2016) and 4.1 billion (zircon graphite, 2015); the 3.4-billion-year fossils remain the firmest.
- Tree of life. The discovery of Asgard archaea (from 2015; first cultured in 2020) supports a two-domain tree in which eukaryotes arise within archaea, revising Fig. 4.
- LUCA. Far from dissolving, LUCA has been sharpened: a 2024 study (Moody et al.) dates it to about 4.2 billion years with some 2,600 proteins, a fairly complex prokaryote.
- Prebiotic chemistry. Sutherland's cyanosulfidic network (2015) and Carell's purine and pyrimidine routes (2016-19) went far beyond one nucleotide. Pross's point that building blocks are not a recipe still stands.
- Sample of one. Over 6,000 exoplanets are confirmed (2025); no biosignature claim has survived scrutiny.
Biology's Crisis of Identity
Biology's three core questions, what life is, how it emerged and how to make it, are locked together, and none is answered. Molecular biology's triumphs, culminating in the human genome, exposed rather than cured our ignorance, because life's essence lies in its organization, not its parts. Pross surveys the escape routes tried so far, systems biology, non-equilibrium thermodynamics and mathematical complexity, and finds that none has cracked the problem.
Three questions, one knot
The book's Fig. 5 draws the three questions as a triangle. Answering any one requires the other two: we cannot make life because we do not know what it is, and we do not know what it is because we do not understand how it emerged. After sixty years of molecular biology, what biology claims to study is still obscure. This is not, Pross insists, a chemist trespassing; Carl Woese wrote in an "almost messianic" article that biology is no better understood in principle than physics a century ago, when the big problems seemed solved and only details remained. "Déjà vu!" Woese, a pioneer of the molecular approach, seemed to have lost faith in it. Paradoxically, it was the flood of molecular knowledge that revealed how ignorant we are.
From Darwin to the genome
Darwin moved biology from the supernatural to the natural world, but the path was rough:
- Delayed acceptance. Natural selection was not fully accepted until the 1930s, almost eighty years after Origin, when the modern evolutionary synthesis merged Darwin with Mendelian and population genetics and supplied the mechanism.
- The molecular revolution. From 1953: DNA replication, RNA transcription, protein translation, the ribosome, and a string of Nobels leading to what Walter Gilbert called the Holy Grail: the sequence of all 3 billion bases of human DNA.
- The genome moment. On completion in 2000, Bill Clinton declared at the White House that "today we are learning the language in which God created life" and promised a revolution in treating "most, if not all" human diseases; personalized medicine by 2010.
The reductionist dream seemed realized: humanity reduced to a string of 3 billion letters, the rest mere details, just as physics felt in the 1890s. The promised rewards did not arrive. The gap between the sequence and its meaning is cavernous. Stuart Kauffman, in Investigations, put it plainly: we know many parts and processes, "but what makes a cell alive is still not clear to us. The center is still mysterious."
The problem is organizational complexity. Tibor Gánti, the Hungarian chemical engineer, said it over 35 years earlier: living systems' special properties arise "not from the substances of the system, but from their special organizational manner". It is the organization of life, not the stuff of life, that makes life unique, and reductionist molecular biology has not explained that organization.
Escape route 1: systems biology
One response was to declare that biology needs its own philosophy of science, irreducible to physics for unspecified reasons: divide and conquer. That mood fed systems biology, which studies how cellular components interact as a system, on the belief that general features such as network topology reveal behaviour.
Pross's verdict: no nirvana. No general rules of complex systems have been found, and systems insight without attention to the components is limited; holism is largely "reductionism dressed up" (chapter 3). Worse, systems biology falls back on "emergent properties" whenever explanation fails. That label creates an illusion of explanation: an unexplained phenomenon keeps attracting attention, but one filed as "emergent" looks settled. Hence the near-total lack of interest in the physical basis of teleonomy, which Monod called the "central problem of biology". The question may sound philosophical; it is not. Answering how purpose and function arise spontaneously would join chemistry, the objective world, to biology, the teleonomic world. Darwinism unified biology internally, but the price was isolation from the physical sciences.
Escape route 2: non-equilibrium thermodynamics
Ilya Prigogine, the Belgian physical chemist, developed non-equilibrium thermodynamics in the 1950s and 1960s from systems such as hurricanes, whirlpools and vortices. The claim was that these shed light on how life's non-equilibrium organization arose naturally.
Pull the plug and the structureless water spontaneously organizes into a vortex, a dissipative structure. Both vortex and cell are non-equilibrium structures that must keep consuming energy to persist, so perhaps organization in an open, energy-consuming system explains life's organization. These ideas were popular 20-30 years before the book, then faded, because the analogy produced no biological insights or novel predictions. John Collier (philosopher, Calgary) noted there is no evidence that non-equilibrium thermodynamics applies to biology in a non-trivial way.
Escape route 3: mathematical complexity
In 1970 Princeton mathematician John Conway invented the Game of Life. Squares on a grid are alive (black) or dead (white), and each generation updates every square from its eight neighbours:
- Underpopulation. A live cell with fewer than two live neighbours dies.
- Survival. A live cell with two or three live neighbours lives on.
- Overcrowding. A live cell with more than three live neighbours dies.
- Birth. A dead cell with exactly three live neighbours comes alive.
Some starts are frozen (a 2 × 2 block never changes), some vanish, and some explode into strikingly complex patterns. The lesson, simple rules can generate complexity, is real; Pross promises that real life is governed by a simple rule too. But the game offered no direct insight into living systems.
| Approach | What it offered | Pross's verdict |
|---|---|---|
| Molecular biology | Parts and mechanisms in detail | "Been there, done that"; no forest |
| Systems biology | Networks and interactions | Jury out; no breakthrough imminent |
| Non-equilibrium thermodynamics | Order from energy flow | A dead end for biology |
| Conway's Life | Simple rules, complex outcomes | Instructive in general, silent on life |
The way forward, Pross says, lies in the final two chapters: a newly founded area of chemistry that can at last give concrete answers.
- The genome. Clinton's 2000 event marked a draft; the "finished" sequence came in 2003, and the first truly gap-free (telomere-to-telomere) human genome only in 2022. Pross's point about the gulf between sequence and understanding has largely held.
- Non-equilibrium physics revived. Pross's obituary was premature: Jeremy England's dissipative adaptation (from 2013) and later work on driven self-assembly and the thermodynamics of self-replication brought non-equilibrium physics back into origin-of-life debates, as a rival to DKS rather than an ally.
- Gánti. His chemoton model (1971) of metabolism, template and membrane is now widely cited as a blueprint for minimal life.
Biology is Chemistry
The book's central chapter. Pross argues that abiogenesis and biological evolution are one continuous process, driven by one force, the drive toward greater dynamic kinetic stability. Laboratory replicators already show selection, ecological niche-splitting, cooperation and simplification, so Darwinian concepts can be translated into chemistry: natural selection is kinetic selection, fitness is DKS, information is specific catalysis. Add complexification to the evolutionary sequence and an energy-gathering capability to the replicator, and Schrödinger's far-from-equilibrium puzzle has a feasible solution.
Systems chemistry: building from the bottom
Many biologists say reduction has hit its limits in biology. Pross disagrees: reduction can be applied to biology at the global, holistic level, and biology is just chemistry, more precisely a sub-branch of chemistry: replicative chemistry.
Systems chemistry got its name as a play on systems biology. Where systems biology works top-down, starting from today's cells and asking how the parts make the whole, systems chemistry works bottom-up: it studies simple chemical systems that self-replicate and asks what rules, if any, govern their complexification toward biology. Two arguments favour bottom-up:
- It retraces a real path. If life came from non-life, it began simple and grew complex step by step. The bottom-up route is not a thought experiment; a real low-complexity replicator actually travelled it, and a well-defined process suggests a driving force to be found.
- Simple prototypes explain more. To learn what an aircraft is, do not dismantle a Boeing 747 with some 6 million parts and 200 kilometres of wiring, including seat-back screens, call buttons and ovens irrelevant to flight. Study the Wright brothers' 1903 Flyer, where every part matters. Simple replicating systems are life's Wright Flyer.
Two phases or one?
The conventional picture (the book's Fig. 6) has two stages: a contentious chemical phase (abiogenesis) ending in a simple life form able to replicate and evolve in a self-sustained way, then a biological phase governed by Darwinian evolution, broadly unshakeable. Pross drops what he calls his bombshell: it is one process, and not merely in the trivial sense that one followed the other in time. One chemical mechanism runs through both. That implies a broader principle hidden inside Darwin's theory that covers non-living replicators. Why has it been seen as two stages? Ignorance: we know one mechanism and not the other, and ignorance is a poor basis for classification.
THE EVIDENCE FROM THE TEST TUBE
- Evolution. Spiegelman's Qβ RNA evolved by replication, mutation, selection, the sine qua non of biology, at the level of molecules. Molecular evolution has since been seen by many groups and is experimentally uncontroversial.
- Ecology. Gerald Joyce (Scripps) showed in 2009 that the ecological competitive exclusion principle ("complete competitors cannot coexist"; ecological differentiation is the condition for coexistence) holds for molecules.
- Cooperation. Joyce's cross-catalytic RNA pair replicated far better than any single replicator.
- Simplification. Evolution sometimes simplifies, in chemistry as in biology.
On the Galápagos (visited by Darwin in 1835), finches from one ancestor diverged: ground finches with strong beaks for nuts and seeds, tree finches with sharp beaks for insects, coexisting because they eat different things. Joyce let two RNAs, RNA-1 and RNA-2, replicate on one substrate: the better replicator drove the other extinct, and switching substrate reversed the winner. Given five substrates, both at first used all five; over time each specialized on a different one and they coexisted. Darwin's finches are doing what molecules began doing billions of years ago.
COMPLEXIFICATION AND COOPERATION
Over evolutionary time complexity has risen: prokaryotes perhaps 4 billion years ago, eukaryotes with nuclei and organelles about 2 billion years later, multicellular plants and animals about 600 million years ago (though bacteria and archaea, the majority of life, have stayed "happily simple"). The chemical phase, whatever its details, also turned something simple into a complex cell. Since chemical laws have not changed, today's systems chemistry can tell us what prebiotic replicators could do.
What it shows first is that getting single molecules to self-replicate is hard, a standard argument against replication first. Joyce built an RNA T, made of two segments A and B, that templated the joining of free A and B into new T without enzymes. It was poor: seventeen hours to double, and it stalled after two rounds because of side reactions, even with fresh A and B. Then Joyce switched to two RNAs selected to make each other: cross-catalysis. The pair doubled in about one hour and kept going indefinitely while building blocks lasted.
Neither molecule copied itself; the system as a whole self-replicated, just as a cell replicates holistically rather than part by part. What one simple replicator could do only poorly, a slightly more complex network did well: complexification enhanced replicative ability. This "I'll scratch your back if you scratch mine" is the chemical root of symbiosis, endemic in biology.
SIMPLIFICATION TOO
Evolution is not only complexification. Cave crickets and cavefish lose their eyes in the dark; Spiegelman's Qβ RNA dropped genome segments useless in a resource-rich test tube. Simplification in both worlds strengthens the case for unity, but over the long run complexification is the underlying tendency in both.
THE MISSING STEP
Classical theory runs replication, mutation, selection, evolution. Pross inserts the overlooked step: replication, mutation, complexification, selection, evolution, valid for chemical and biological phases alike. Complexification, mainly by building networks, is how simple chemical replicators become biological ones.
If the phases are one, chemical insight can illuminate biology and 150 years of Darwinian insight can illuminate prebiotic chemistry. Darwin's guess at a general law of life (prologue) can now, Pross says, rest on hard facts from systems chemists.
One language: chemistry
A single process needs a single language, and it must be the lower-level one. Weinberg's "explanatory arrows always point downward" again: a molecular explanation of schizophrenia would bring drug companies to your door, but explaining molecules psychologically ("neurotic molecules") would bring only derision. So biological terms such as fitness, natural selection, adaptation, cooperation, information should not be used to explain chemical phenomena; you will not find them in chemistry textbooks. The whole of Fig. 6 must be translated into chemistry.
| Biological term | Chemical root | What the translation adds |
|---|---|---|
| Natural selection | Kinetic selection | Rate equations predict who wins, how fast, when coexistence is possible |
| Fitness | Dynamic kinetic stability | Fitness belongs to populations, depends on context |
| Maximizing fitness | Maximizing DKS | A driving force for the whole process |
| Survival of the fittest | Drift to more persistent replicators | Selection is the rudder, not the engine |
| Information | Specific catalysis | Information arises chemically, at an energy cost |
NATURAL SELECTION = KINETIC SELECTION
When replicators compete for building blocks, chemical kinetics, going back about a century to Alfred Lotka, predicts the outcome by solving rate equations: in most cases the faster replicator drives the slower to extinction. Chemists call this kinetic selection, "the faster one wins". It is the competitive exclusion principle in chemical dress. Hence natural selection = kinetic selection: the biological term emulates the chemical one. The chemical version is deeper because chemical systems are simple enough to break into individual reaction steps, so it can say how long one replicator takes to beat another and under what conditions they coexist.
FITNESS = DYNAMIC KINETIC STABILITY
Darwin's fitness, the capacity to survive and reproduce, has fractured into absolute, relative, inclusive and ecological fitness under efforts to quantify it. Pross's translation: fitness = DKS. Calling an entity fit means its population persists through ongoing replication. Since DKS has no meaning for an individual, fitness is a population property. Individuals are born and die; evolution operates only on populations. Focus on the individual and you miss life's dynamic essence (and, chapter 8 will ask, do individuals even exist?).
Manfred Eigen and Peter Schuster's quasispecies theory (1970s) supports this. Picture a fitness surface, a topographic map: horizontal axes for sequence (changed by mutation), vertical axis for fitness, peaks for fast replicators. A replicating RNA explores it like a hiker seeking the highest peak. Eigen and Schuster found that what results is not one sequence but a cloud of variants around a wild type, moving like a flock of birds across the map. The fittest population, the quasispecies, is selected, not the fittest sequence. A breakthrough mutant is as likely to come from a slow variant as a fast one, so the road to a fitter population can pass through a less fit individual, and heterogeneous populations evolve better. The individual is "a transient water droplet in the fountain of life".
DKS also differs from ordinary stability in kind:
- Thermodynamic stability is intrinsic. Water's stability relative to H₂ + O₂ barely depends on what else is present; it is measured in closed systems.
- DKS is circumstantial. It is set by reaction rates, is sensitive to conditions, and can only be assessed in open systems fed with energy and resources. When Spiegelman added ethidium bromide, a different sequence won; add chlorine to a pond and its bacteria's DKS falls to zero.
CAN DKS BE MEASURED?
Only partly. Relative replication rates measure relative DKS for populations sharing a resource, such as two RNAs competing for the same activated nucleotides. Comparing E. Coli and a camel is meaningless. And because DKS is circumstantial, quantifying it is "like preparing for an exam where the answers keep changing". That explains why fitness has resisted quantification: some things that count cannot be counted. Two crude gauges exist:
- Population size. Large steady-state populations withstand change: cockroaches and mosquitoes beat pandas. "Replication is ultimately a numbers game."
- Persistence time. Cyanobacteria have lasted billions of years; modern humans only 150,000-200,000.
The driving force: maximizing DKS
Nature's processes have driving forces: gravity for rivers, rain, avalanches and apples; the Second Law for chemical reactions. "Force" here means a pattern inferred from its action (chapter 3). For replicators the observed tendency to become better replicators reveals the force: maximizing fitness = maximizing DKS.
- One force, both phases. Abiogenesis and evolution both express the drive to greater DKS, so the emergence of life was not a heap of contingent accidents but a coherent process. That is why the two phases are one.
- Selection is a rudder. Natural selection is not the driving force; it only selects, steering populations toward higher DKS by removing what lowers it.
- Complexification is the main mechanism. Invisible over short spans, like ageing day by day, it is unmistakable over billions of years: from a fragile replicator to elephants.
The contrast is stark. Systems chemists struggle to coax temperamental replicating molecules into copying in a sophisticated lab; a pinch of backyard soil holds billions of bacteria replicating with "no chemist in charge, no lab, no postdocs". Bacteria are robust, high-DKS replicators, and they got that way through complexification. The first step on that road is visible in Joyce's two-molecule network.
Information is specific catalysis
Information saturates modern biology: DNA replication preserves it; transcription and translation, the central dogma, express it. Yet chemistry textbooks never mention it. If biology is chemistry, where is information in chemical terms?
Pross's answer: DNA is an autocatalyst (it templates its own copying) and, through messenger RNA and the ribosome, a highly specific catalyst for making other molecules: change the sequence and you get a different protein. Biological information is, in chemical terms, specific catalysis. Over evolution a primordial nucleic-acid autocatalyst, perhaps first catalysing simple peptides, became ever more efficient and specific, culminating in the genetic code, driven by the DKS imperative.
Ordered DNA is thermodynamically unstable and the Second Law degrades information, but creating information is legal if the energy cost is paid, as Pross pays it writing this book. Metabolism pays life's bill. So "how did information arise?" is just Schrödinger's question restated: how did far-from-equilibrium systems arise?
A general theory of evolution
- Why (driving force). The drive toward greater replicator DKS.
- Start. An oligomeric replicator prone to imperfect copying; RNA or something like it, though its exact identity is not needed for the principle.
- Replication. Alone or in a minimal network, it tends to raise its DKS.
- Mutation. Copying errors, plus horizontal gene transfer, generate diversity.
- Complexification. Replicators interact with other materials, including non-replicating catalytic peptides, in co-evolution, building ever larger networks that stay holistically autocatalytic.
- Selection. Kinetic selection shifts the population toward members that raise its DKS.
- Result. Repeated cycles give evolution.
The material world thus splits into two parallel worlds: the "regular" chemical world governed by the Second Law, and the replicative world governed by its analogue, the drive to DKS. The chemistry of the replicative world is called biology.
How metabolism arose: the analogue wins
If two stability laws pull in opposite directions, which wins? Surprisingly, the Second Law analogue, though without ever breaking the Second Law. The trick is an energy-gathering system, which lets a replicator have its cake and eat it.
Emmanuel Tannenbaum, Nathaniel Wagner and Pross (Ben-Gurion University) simulated a replicator that, by chance mutation, gained a way to capture energy, say light, in a primitive photosynthesis. It outcompeted and drove to extinction a replicator without that ability, even when intrinsically slower.
The reason: building blocks must be activated (made high-energy) to link up on the template, a Second Law requirement. Activated blocks are scarce compared with inactive ones, so a non-metabolic replicator runs dry and stops. A metabolic replicator transfers captured energy to blocks bound to it, activating them, and carries on. Energy-gathering frees a replicator from the Second Law the way an engine frees a car from rolling only downhill. So there is a second route to higher DKS besides structural complexification: metabolic complexification.
Pross suggests the moment a "downhill" replicator acquired an energy-gathering capability could be thought of as the moment life began. From then on it could pursue its replicative "agenda" despite the energy cost, reconciling DKS with the Second Law. Thermodynamically unstable but DKS-stable entities can emerge naturally: Schrödinger's puzzle has a feasible solution.
Replication and metabolism together
Joyce's result also settles the old dichotomy. A single RNA could not replicate robustly; a two-molecule cycle could. So template autocatalysis and cycle formation were both needed, probably in step: complexification (cycles) could not happen without replication, and replication without complexification had nowhere to go. Pross offers a "Solomon-like" verdict: replace replication-first and metabolism-first with replication and metabolism together.
- Otto lab (Groningen). Sijbren Otto's self-assembling disulfide macrocycle replicators have shown diversification into distinct replicator "species" (2016), the emergence of catalytic function in replicators, and in 2023 light-driven eco-evolutionary dynamics in a flow reactor, with replicators reshaping their own environment.
- RNA replicators. Joyce's group used a polymerase ribozyme to copy and evolve other functional RNAs (2024); Holliger's Cambridge lab described QT45, a 45-nucleotide ribozyme that can synthesize both itself and its complement in ice (Science, 2026), though not yet in one continuous cycle.
- DKS work. Pross and Robert Pascal extended the theory (2013-23) and co-edited Evolution "On Purpose" (2023).
The dictionary is illuminating but lossy. Fitness in biology includes frequency dependence, inclusive fitness and trade-offs that "replication rate minus decay" does not capture. "Information = specific catalysis" sets aside the arbitrary, symbolic character of the genetic code that many see as the real puzzle. The energy-capture result is a simulation, not a mechanism for the origin of metabolism. And "complexification as the underlying tendency" faces Gould's objection that rising maximum complexity can be a passive spread away from a lower limit.
What is Life?
Pross assembles his theory and tests it against the six strange properties of chapter 1. Life is replicative chemistry: the network of reactions produced when exponential replication drives simple oligomers toward ever greater dynamic kinetic stability. Complexity, thermodynamic instability, turnover, diversity, homochirality and purpose all follow. The theory also implies that abiogenesis is solved in principle, that life elsewhere would look familiar, that making life must proceed step by step, and that individuals are nodes in a network rather than independent things.
Why a separate theory of life?
There is already a theory of all matter: quantum theory, which in principle predicts any chemical system's behaviour. In practice it handles only moderate-sized systems; ask a computational quantum chemist to treat a whole cell and "he will likely just grimace and walk away". So a theory of life is needed: separate but not independent, a smaller Russian doll inside the theory-of-matter doll. Its premise is that life began simple and its essence reflects those beginnings, so the layers of complexity must be peeled away along a reverse time axis until the core appears.
That core is systems chemistry, which shows Darwinism to be part of a general chemical theory of evolution covering living and non-living systems. Abiogenesis is the low-complexity phase, biological evolution the high-complexity phase. The trigger was the appearance of a simple replicating system, which opened the door to replicative chemistry and its other kind of stability.
THE POWER OF NUMBERS
What makes replication special is not what it produces but how much. A single replicating molecule weighing 10⁻²¹ grams, copying once a minute, would in principle outweigh the entire universe in under five hours. That kinetic power turns the usual rules of chemistry upside down: ordinary matter is stable if it does not react; replicating matter is stable if it does react to make more of itself, and better replicators are more stable. Populations of poorer replicators turn into better ones, the Second Law analogue, always within the Second Law itself.
Life is a self-sustaining kinetically stable dynamic reaction network derived from the replication reaction. Self-sustaining: it has an energy-gathering capability, satisfying the Second Law. Kinetically stable and dynamic: the DKS kind of stability. Network and replication: its structure and origin. Death is reversion from the kinetic, replicative world to the thermodynamic world of regular chemistry.
Biology is thus a particularly complex replicative chemistry, and the living state is a new state of matter, the replicative state. Life is the network of chemical reactions that emerges from the continuing cycle of replication, mutation, complexification and selection acting on certain chain-like molecules (on Earth, nucleic acids); it is the chemical consequence of exponential growth. Other chemistries might do the same, though no one has yet tested it.
OLD THEORY, NO QUANTUM MYSTERY
The "hard theory" is old: Thomas Malthus's Essay on the Principle of Population (1798) grasped exponentials, and Alfred Lotka's kinetics (from 1910) applied them to chemical and biological systems. No quantum mechanics is needed: life is a classical phenomenon, and past physicists' appeals to quantum strangeness look unnecessary. Complexity hid the insights of Malthus, Lotka, Troland, Eigen and Schuster. The relationship is now clear: complexity is not the cause or essence of life but its consequence. Replication induced complexity, not the reverse.
The six properties explained
| Property (ch. 1) | The puzzle | DKS explanation |
|---|---|---|
| Complexity | How did organization arise? | Complexification raises DKS; high complexity and high DKS go together |
| Instability | Why is the world full of unstable things? | They are DKS-stable; replicating requires reactivity |
| Dynamic nature | Why constant turnover? | Stable replicator populations need formation balanced by decay |
| Diversity | Why do many come from few? | Replicator space is divergent; regular chemistry convergent |
| Homochirality | How did it arise and persist? | Autocatalytic amplification; homochiral systems replicate better |
| Teleonomy | How can matter have an agenda? | Energy-gathering replicators follow the kinetic, not thermodynamic, directive |
COMPLEXITY
Ordinary aggregation, such as water freezing or a solid crystallizing, happens because the aggregate is thermodynamically more stable, less reactive. In the replicative world aggregation follows DKS: thermodynamics contributes but only facilitates. Joyce's two RNAs forming a small replicating network are the simplest case. A fragile replicator complexifies step by step, each step a slightly better replicator, by Woody Allen's "whatever works" rule. Where simplification raises DKS, nature simplifies instead. Billions of years later: staggering complexity with extraordinary DKS.
INSTABILITY
Like the hovering bird, every organism is thermodynamically unstable, yet unstable entities fill every niche. They are stable in the DKS sense, and they must be thermodynamically unstable, because DKS demands continual reaction; balls at the bottom of a slope go nowhere. The energy-gathering replicator, a car with an engine, reconciles the two. Once it arose by chance mutation it drove its predecessors extinct, which is why every living system without exception has an energy-gathering system: photosynthesis in plants and some bacteria, the Krebs (citric acid) cycle for breaking down organic matter in animals. Robert Pascal has begun exploring the chemistry by which early metabolism could have arisen.
DYNAMIC NATURE
This is the easiest. Replication is unsustainable, so any stable replicating system, "molecules, microbes, or monkeys", must balance generation and decay: the population persists, the individuals turn over, like water in a fountain, at every level from molecules to organisms. Death is part of the life strategy. Steve Jobs told Stanford graduates in 2005 that death "is very likely the single best invention of Life. It is Life's change agent." Eternal life is an oxymoron.
DIVERSITY
Darwin left his Principle of Divergence unresolved. Pross's answer lies in the topology of the two chemical worlds.
Regular chemistry: convergent Systems head for their thermodynamic sink. Burn any hydrocarbon mixture and you get CO₂ and water. All roads lead to Rome, which is why chemists can predict products. Systems can be closed.
Replicative chemistry: divergent Replicators must stay open to building blocks and energy. The route to higher DKS depends on what is available here and now: X may pair with Y, or with Z. Many paths exist, so populations diversify.
Divergence forward is convergence backward. That is why phylogeny and fossils can trace life back to three kingdoms and LUCA, and why we can say nothing about where evolution will go. Yogi Berra: "If you don't know where you are going you will wind up somewhere else."
HOMOCHIRALITY
Making a chiral product from non-chiral starting materials normally gives a 50:50 mix. In 1995 Kenso Soai found a reaction yielding essentially one hand only from non-chiral reagents, as startling as 999 heads in 1,000 tosses. The reaction is autocatalytic: a tiny initial excess of one hand is amplified exponentially to near 100 per cent purity. The same kinetic power that started life could have made it single-handed.
Maintenance follows from DKS. Homochirality is less stable thermodynamically, but life's reactions need precise lock-and-key fits; in a mixed system "half the keys" would not fit their locks. Homochiral systems are better replicators, hence more stable in the DKS sense.
TELEONOMY
A simple replicator without energy capture follows the thermodynamic directive, like a car without an engine that can only roll downhill. Once it gains an energy-gathering capability it is freed to follow the kinetic directive, the drive toward greater DKS, even if that means going partly uphill. We read such behaviour as purposeful. Monod's paradox dissolves: in the regular chemical world thermodynamics dominates and behaviour looks objective; in the replicating world kinetics dominates and behaviour looks purposeful.
Beyond the six
CONSCIOUSNESS
Consciousness is a property of advanced life, not an essential one, so Pross sets it aside, while noting how little we understand it. Evolution exploits every property of matter that helps replication: hardness in bone, firm flexibility in cartilage, liquidity in blood, transparency in crystallin of the eye lens, electrical conduction. Matter organized in certain ways is self-aware, and evolution used that too. The method should be the same as for abiogenesis: start simple, from rudimentary neural activity, and follow it upward.
HOW WOULD ALIEN LIFE LOOK?
If life arose here from non-life, it can arise elsewhere, perhaps on chemistry other than the nucleic acid-protein duo, since chemical properties belong to groups of substances rather than single ones. Pross's answer, half in jest: alien life would look just like ours. Life's forms already range from bacteria to blue whales, and form follows function, not material. Cars of fibreglass, aluminium or steel look alike because all need a shell, cabin, windows and wheels, whether made in the US or China, electric or petrol. Alien replicators evolving toward higher DKS would rediscover networks and probably cells. The theory is about process, not material.
SYNTHESIZING LIFE
Life is easy to destroy and very hard to make, because the problem is organization, not material. Pross's image is the juggler: a man juggling five balls and a man standing beside five balls on the ground are materially identical. One push turns the first into the second, the metaphor for death. But throwing five balls at someone at once will not make him juggle. Mix all the components of a cell and at best you get a dead cell, a thermodynamic aggregate, not a far-from-equilibrium dynamic system.
The strategy must mirror evolution: toss one ball, then another, step by step: enter the replicative dynamic state at low complexity and complexify. Even simplest life is "far more than just a replicating entity in a bag"; if much simpler free-living forms were physically possible, we would see them. Sijbren Otto and his student Elio Mattia at Groningen have begun exploring how to create dynamic kinetically stable chemical systems. Pross judges a lifelike, self-sustaining replicating aggregate "highly ambitious" for now.
HOW DID LIFE EMERGE?
If abiogenesis and evolution are one process, and we broadly understand evolution, then we understand abiogenesis in the ahistorical sense. The answer is "breathtakingly simple": the kinetic power of replication acting on simple, unidentified oligomeric replicators (RNA or RNA-like), which complexified because that raised their DKS. The what, where and when will "tease and torment us", but Darwin's theory also never gave the specific history; that was left to palaeontology and phylogeny. Darwin's 1882 letter to George Wallich, predicting that life would prove "part, or consequence, of some general law", looks almost clairvoyant, vindicated by Joyce, von Kiedrowski, Reza Ghadiri, Gonen Ashkenasy, Otto and others.
Life as a network
Complexification is network formation: from simple to complex reaction networks that remain holistically self-replicating. Life is more process than thing; Carl Woese and Nigel Goldenfeld: "Biology is a study, not in being, but in becoming." The medium is water, the "cosmic juice", whose unusual properties let the network form.
DO INDIVIDUALS EXIST?
The network view makes individuality doubtful:
- Bacteria. Some species switch from free swarms to a multicellular lump when resources run short; cells constantly signal chemically; biofilms coordinate. "Bacteria are more a network than a set of individuals."
- Early cells. Woese argued early cells were communal, dominated by horizontal gene transfer; looser, modular networks of discrete cells came later, a phase transition. Modular networks survive attack better, so individuality is a life strategy, not a life characteristic.
- Humans. About 10¹³ human cells, with ten times as many bacterial cells, hundreds of species: a superorganism, its microbiome called the "forgotten organ".
- Plants. They depend on soil and root bacteria to fix nitrogen.
- Viruses. Gut bacteria host viruses; giant viruses larger than small bacteria are themselves infected by small viruses. Russian dolls all the way down.
- Upward. Individuals sit in families, communities and societies. Sex shows we are reproductively incomplete; "the individual has no future, literally". We think we are separate, "but we are one".
So the biosphere is an ever-expanding network, not an invasion of billions of individuals. The old puzzles ease: a mule or lone rabbit cannot reproduce but is still part of the replicative network, a dead-end road is still a road, and mules are replicative entities because of how they came to be. Whether viruses are alive is "more philosophic and linguistic than scientific"; they lack independent metabolism but are integral to the network.
Chemistry and biology merge
From Darwin to systems chemistry, Pross concludes, biology and chemistry are becoming one, the integration Darwin foresaw 130 years earlier. Within science's limits we can now begin to say what life is, why it emerged, how we, "a twiglet on the tree of life", relate to the universe, and why, despite Darwinism's harshness, we are committed to one another. Whether that is hope for Hawking's "chemical scum", only time will tell.
- "Largely resolved" is overreach. DKS names a direction, not a pathway; the hard step, an open-ended replicator arising from prebiotic chemistry, is still undemonstrated.
- Teleonomy. Energy capture explains why replicators can climb uphill, not obviously why we should call that agency. Pross pressed the case later (Purpose & Desire, 2018); many remain unconvinced.
- Soai. Its organozinc chemistry is not prebiotic; it proves amplification is possible, not what happened.
- Numbers. The 10:1 bacteria ratio is now about 1:1 (2016).
- Synthesis since. JCVI-syn3.0 (2016, 473 genes) is life built top-down from biology. Bottom-up, Otto's replicators evolve and Holliger's QT45 ribozyme (2026) nearly self-replicates, but no chemical system yet lives.
Master Takeaways
- Life is replicative chemistry. Biology is the most complex branch of the chemistry of self-replicating systems, and the living state is a distinct replicative state of matter.
- There are two kinds of stability. Ordinary matter is stable if it does not react; replicating populations are stable (persistent) if they keep reacting to make more of themselves. Pross calls the second kind dynamic kinetic stability (DKS).
- Exponential growth is the root of it all. Replication is autocatalytic, so one grain becomes 2⁶⁴ − 1 grains on a chessboard; one molecule copying each minute would outweigh the universe in under five hours.
- Abiogenesis and evolution are one process. The chemical phase is the low-complexity part, the biological phase the high-complexity part, both driven by the push toward greater DKS.
- Darwin translates into chemistry. Natural selection = kinetic selection, fitness = DKS, maximizing fitness = maximizing DKS, information = specific catalysis.
- Energy capture is where life starts. A replicator that gathers energy can climb thermodynamically uphill and out-compete faster rivals; purposeful-looking behaviour follows from that kinetic freedom, dissolving Monod's paradox.
- Complexification is the missing step. The evolutionary sequence is replication, mutation, complexification, selection, evolution, with complexification mostly meaning network formation.
- Cooperation pays from the start. Joyce's cross-catalytic RNA pair doubled in about an hour and ran indefinitely, where a single self-replicator took 17 hours and stalled after two rounds.
- Ecology exists at the molecular level. Joyce's RNAs obeyed the competitive exclusion principle and partitioned five substrates like Darwin's finches.
- Fitness is a population property. DKS means nothing for an individual; Eigen and Schuster's quasispecies shows the fittest cloud of variants is selected, not the fittest sequence.
- DKS is circumstantial. Unlike thermodynamic stability it depends on conditions, so comparisons only make sense for replicators sharing a resource; that is why fitness resists quantification.
- Selection is a rudder, not an engine. The driving force is the drive to higher DKS; selection merely prunes.
- Replicator space diverges. Regular chemistry converges on thermodynamic sinks; open replicating systems branch according to what is locally available, which explains diversity and why phylogeny works backward but the future cannot be predicted.
- Turnover and death are built in. A persistent replicating population must balance birth and decay; eternal life is an oxymoron.
- Homochirality is kinetic. Autocatalysis can amplify a tiny chiral excess (Soai), and homochiral systems replicate better, so they win on DKS despite losing on thermodynamics.
- Complexity is a consequence, not a cause. Replication induced complexity; no quantum mystery is needed.
- Both origin camps fail for the same reason. Neither replication-first nor metabolism-first explains how downhill chemistry yields far-from-equilibrium organization; Pross proposes replication and metabolism together.
- The ahistorical "why" matters more than the historical "how". Fossils, phylogeny and prebiotic chemistry cannot reach abiogenesis; studying replicating systems today can.
- You cannot prove a reaction impossible. Sutherland's nucleotide synthesis refuted decades of "it can't be done"; absence of evidence is not evidence of absence.
- Definitions come after theories. Following Cleland and Chyba, a definition of life before a theory is a field guide, not an explanation.
- "Emergent property" can be a dead end. Labelling teleonomy emergent created an illusion of explanation and stalled inquiry.
- Individuality is a strategy. Bacteria, holobionts and sexual organisms show life is a network; separate individuals are one of evolution's tricks for robustness.
- Life must be built step by step. Like teaching a juggler, enter the replicative state at low complexity and add one ball at a time; mixing a cell's parts yields only a dead cell.
- Process, not material. Alien life on a different chemistry would converge on networks, cells and familiar forms.
Frameworks & mental models
| Name | What it says | Use it when |
|---|---|---|
| Two stabilities | Static (thermodynamic) versus dynamic kinetic stability | Asking why something persists |
| Replicator selection rule | Replicators move toward greater DKS, inside the Second Law | Predicting how self-copying systems change |
| Russian dolls | Specific rules operate within general laws | A true but useless explanation is offered |
| Historical vs ahistorical | "How did it happen" versus "why does it happen" | Choosing a tractable research question |
| Extended evolution sequence | Replication, mutation, complexification, selection, evolution | Explaining growth of complexity |
| Biology-to-chemistry dictionary | Selection, fitness, information as kinetics, DKS, catalysis | Seeking a deeper, quantifiable explanation |
| Convergent vs divergent space | Closed systems converge; open replicators diverge | Explaining diversity or unpredictability |
| Understanding test | Explain in lower-level terms and gain control | Judging whether a field really understands |
| Juggler strategy | Dynamic states are entered stepwise, destroyed at once | Building or restoring dynamic systems |
Pross offers a clear, unifying idea, and DKS has become a recognized position in origin-of-life theory. But the book claims more than it shows. DKS is a direction, not a mechanism: it does not say which chemistry produced the first open-ended replicator, and Pross concedes it can barely be quantified, which leaves it close to a chemical renaming of fitness. The dismissal of historical research looks premature: since 2012 prebiotic chemistry (Sutherland, Carell), phylogenomics (a dated, gene-rich LUCA, Asgard archaea) and rival physical theories (England's dissipative adaptation, assembly theory's 2023 claims and the backlash) have all advanced. Some numbers (the 10:1 microbiome ratio) are outdated. The "solution" to teleonomy explains apparent purpose rather than agency. And no lab has yet built the living chemical system the theory says must be built step by step.
Who's who
| Name | Role | Why they matter |
|---|---|---|
| Erwin Schrödinger | Physicist, What is Life? (1944) | Posed the question; suspected "other laws of physics" |
| Charles Darwin | Naturalist | Natural selection; foresaw a "general law" of life (1882) |
| Jacques Monod | Biologist, Chance and Necessity (1971) | Framed teleonomy as biology's central contradiction |
| Carl Woese | Microbiologist | Discovered Archaea; called for a new biology; communal early life |
| Sol Spiegelman | Molecular biologist | 1967 test-tube RNA replication and evolution ("monster") |
| Günter von Kiedrowski | Chemist | First enzyme-free replicator (1986); named systems chemistry |
| Gerald Joyce | Biochemist, Scripps | RNA niche partitioning and cross-catalytic replicators (2009) |
| Manfred Eigen, Peter Schuster | Chemists | Quasispecies theory; population view of selection |
| Stuart Kauffman | Theoretical biologist | Collectively autocatalytic sets (metabolism first) |
| John Sutherland | Chemist | Prebiotic nucleotide synthesis; co-author with Pross |
| Kenso Soai | Chemist | Autocatalytic chiral amplification (1995) |
| Sijbren Otto | Systems chemist, Groningen | Synthetic replicators that diversify and evolve |
| Cleland and Chyba | Philosopher, astronomer | Theory, not definition, of life |
Connect it
- Persistence by reproduction. Systems that last by constantly replacing their parts (a codebase, a team, a product line) are stable in the DKS sense: judge them by turnover rates and population health, not by any single component.
- Network over node. Pross's point that individuals are nodes in a replicative network maps onto enterprise architecture: resilience comes from loosely coupled, self-sufficient modules, the strategy early cells "discovered".
- Divergence is unpredictable. Open systems fed with new resources branch in ways that can be explained backward but not forecast; plan for optionality rather than a single predicted end state.
- Translate to the lower level. When a high-level label ("emergent", "culture", "AI magic") is doing the explaining, look for the mechanism one level down.
About this book
What Is Life?: How Chemistry Becomes Biology by Addy Pross, 2012. This is a chapter-by-chapter study of the book, with summaries, maps, tables and diagrams; short quotations keep their page references. It is shared free for personal study, is not for sale, and is not endorsed by the author or publisher. Please read and buy the original.
Insight Editions · rajeshrmahapatra.com/insight-editions