Stuart A.Kauffman
Oxford University Press 


Lecturing in Dublin, one of the twentieth century's most famous physicists set the stage of contemporary biology during the war-heavy year of 1944. Given Erwin Schrödinger's towering reputation as the discoverer of the Schrödinger equation, the fundamental formulation of quantum mechanics, his public lectures and subsequent book were bound to draw high attention. But no one, not even Schrödinger himself, was likely to have foreseen the consequences. Schrödinger's "What Is Life?" is credited with inspiring a generation of physicists and biologists to seek the fundamental character of living systems. 

Schrödinger brought quantum mechanics, chemistry, and the still poorly formulated concept of "information" into biology. He is the progenitor of our understanding of DNA and the genetic code. Yet as brilliant as was Schrödinger's insight, I believe he missed the center. Investigations seeks that center and finds, in fact, a mystery.

In my previous two books, I laid out some of the growing reasons to think that evolution was even richer than Darwin supposed. Modern evolutionary theory, based on Darwin's concept of descent with heritable variations that are sifted by natural selection to retain the adaptive changes, has come to view selection as the sole source of order in biological organisms. 

But the snowflake's delicate sixfold symmetry tells us that order can arise with-out the benefit of natural selection. Origins of Order and At Home in the Universe give good grounds to think that much of the order in organisms, from the origin of life itself to the stunning order in the development of a newborn child from a fertilized egg, does not reflect selection alone

Instead, much of the order in organisms, I believe, is self-organized and spontaneous. Self-organization mingles with natural selection in barely under-stood ways to yield the magnificence of our teeming biosphere. We must, therefore, expand evolutionary theory.

Yet we need something far more important than a broadened evolutionary theory. Despite any valid insights in my own two books, and despite the fine work of many others, including the brilliance manifest in the past three decades of molecu-lar biology, the core of life itself remains shrouded from view. We know chunks of molecular machinery, metabolic pathways, means of membrane biosynthesis—we know many of the parts and many of the processes. But what makes a cell alive is still not clear to us. The center is still mysterious.

And so I began my notebook "Investigations" in December of 1994, a full half century after Schrödinger's What Is Life, as an intellectual enterprise unlike any I had undertaken before. Rather bravely and thinking with some presumptuousness of Wittgenstein's famous Philosophical Investigations, which had shattered the philosophical tradition of logical atomism in which he had richly participated, I betook myself to my office at home in Santa Fe and grandly intoned through my fingers onto the computer's disc, "Investigations," on December 4,1994. 

I sensed my long search would uncover issues that were then only dimly visible to me. I hoped the unfolding, ongoing notebook would allow me to find the themes and link them into something that was vast and new but at the time inarticulate.

Two years later, in September of 1996, I published a modestly well-organized version of Investigations as a Santa Fe Institute preprint, launched it onto the web, and put it aside for the time being. I found I had indeed been led into arenas that I had in no way expected, led by a swirl of ever new questions. I put the notebooks aside, but a year later I returned to the swirl, taking up again a struggle to see some-thing that, I think, is right in front of us—always the hardest thing to see. This book is the fruit of these efforts. And this first chapter is but an introduction, in brief, to the themes that will be explained more fully in the following chapters. I would ask the reader to be patient with unfamiliar terms and concepts.

My first efforts had begun with twin questions. First, in addition to the known laws of thermodynamics, could there possibly be a fourth law of thermodynamics for open thermodynamic systems, some law that governs biospheres anywhere in the cosmos or the cosmos itself? 

Second, living entities—bacteria, plants, and ani-mals—manipulate the world on their own behalf: the bacterium swimming up-stream in a glucose gradient that is easily said to be going to get "dinner"; the paramecium, cilia beating like a Roman warship's oars, hot after the bacterium; we humans earning our livings. 
Call the bacterium, paramecium, and us humans "autonomous agents" able to act on our own behalf in an environment.

My second and core question became "What must a physical system be to be an autonomous agent?" Make no mistake, we autonomous agents mutually construct our biosphere, even as we coevolve in it. Why and how this is so is a central subject of all that follows.

From the outset, there were, and remain, reasons for deep skepticism about the enterprise of Investigations. First, there are very strong arguments to say that there can be no general law for open thermodynamic systems. The core argument is sim-ple to state. 

Any computer program is an algorithm that, given data, produces some sequence of output, finite or infinite. Computer programs can always be written in the form of a binary symbol string of 1 and o symbols. All possible bi-nary symbol strings are possible computer programs. Hence, there is a countable, or denumerable, infinity of computer programs. 

A theorem states that for most computer programs, there is no compact description of the printout of the program. Rather, we must just unleash the program and watch it print what it prints. In short, there is no shorter description of the output of the program than that which can be obtained by running the program itself. If by the concept of a "law" we mean a compact description, ahead of time, of what the computer program will print then for any such program, there can be no law that allows us to predict what the program will actually do ahead of the actual running of the program.

The next step is simple. Any such program can be realized on a universal Turing machine such as the familiar computer. But that computer is an open nonequilib-rium thermodynamic system, its openness visibly realized by the plug and power line that connects the computer to the electric power grid. Therefore, and I think this conclusion is cogent, there can be no general law for all possible nonequilib-rium thermodynamic systems.

So why was I conjuring the possibility of a general law for open thermodynamic systems? Clearly, no such general law can hold for all open thermodynamic systems.

But hold a moment. It is we humans who conceived and built the intricate assembly of chips and logic gates that constitute a computer, typically we humans who program it, and we humans who contrived the entire power grid that supplies the electric power to run the computer itself. This assemblage of late-twentieth -century technology did not assemble itself. We built it.

On the other hand no one designed and built the biosphere. The biosphere got itself constructed by the emergence and persistent coevolution of autonomous agents

If there cannot be general laws for all open thermodynamic systems, might there be general laws for thermodynamically open but self-constructing systems such as biospheres? I believe that the answer is yes. Indeed, among those candidate laws to be discussed in this book is a candidate fourth law of thermodynamics for such self-constructing systems.

To roughly state the candidate law, I suspect that biospheres maximize the average secular construction of the diversity of autonomous agents and the ways those agents can make a living to propagate further. In other words, on average, biospheres persistently increase the diversity of what can happen next. In effect, as we shall see later, biospheres may maximize the average sustained growth of their own "dimensionality."

Thus, the enterprise of Investigations soon began to center on the character of the autonomous agents whose coevolution constructs a biosphere. I was gradually led to a labyrinth of issues concerning the core features of autonomous agents able to manipulate the world on their own behalf. It may be that those core features capture a proper definition of life and that definition differs from the one Schrödinger found.

To state my hypothesis abruptly and without preamble, I think an autonomous agent is a self-reproducing system able to perform at least one thermodynamic work cycle. It will require most of this book to unfold the implications of this ten-tative definition.

Following an effort to understand what an autonomous agent might be— which, as just noted, involves the concept of work cycles—I was led to the concepts of work itself, constraints, and work as the constrained release of energy. In turn, this led to the fact that work itself is often used to construct constraints on the release of energy that then constitutes further work. So we confront a virtuous cycle: Work constructs constraints, yet constraints on the release of energy are required for work to be done. 

Here is the heart of a new concept of "organization" that is not covered by our concepts of matter alone, energy alone, entropy alone, or information alone. 

In turn, this led me to wonder about the relation between the emergence of constraints in the universe and in a biosphere, and the diversification of patterns of the constrained release of energy that alone constitute work and the use of that work to bnild still further constraints on the release of energy. How do biospheres construct themselves or how does the universe construct itself?

The considerations above led to the role of Maxwell's demon, one of the major places in physics where matter, energy, work, and information come together. The central point of the demon is that by making measurements on a system, the infor-mation gained can be used to extract work. I made a new distinction between measurements the demon might make that reveal features of nonequilibrium sys-tems that can be used to extract work, and measurements he might make of the nonequilibrium system that cannot be used to extract work. How does the demon know what features to measure? And, in turn, how does work actually come to be extracted by devices that measure and detect displacements from equilibrium from which work can, in principle, be obtained? An example of such a device is a wind-mill pivoting to face the wind, then extracting work by the wind turning its vanes. Other examples are the rhodopsin molecule of a bacterium responding to a photon of light or a chloroplast using the constrained release of the energy of light to con-struct high-energy sugar molecules. How do such devices come into existence in the unfolding universe and in our biosphere? 

How does the vast web of constraint construction and constrained energy release used to construct yet more constraints happen into existence in the biosphere? In the universe itself? 

The answers appear not to be present in contemporary physics, chemistry, or biology. But a coevolving biosphere accomplishes just this coconstruction of propagating organization. Thus, in due course, I struggled with the concept of organization itself, concluding that our concepts of entropy and its negative, Shannon's information theory (which was developed initially to quantify telephonic traffic and had been greatly extended since then) entirely miss the central issues. 

What is happening in a biosphere is that autonomous agents are coconstructing and propagating organizations of work, of constraint construction, and of task completion that continue to propagate and proliferate diversifying organization.

This statement is just plain true. Look out your window, burrow down a foot or so, and try to establish what all the microscopic life is busy doing and building and has done for billions of years, let alone the macroscopic ecosystem of plants, herbi-vores, and carnivores tbat is slipping, sliding, hiding, hunting, bursting with flow-ers and leaves outside your window. So, I think, we lack a concept of propagating organization.

Then too there is the mystery of the emergence of novel functionalities in evolu-tion where none existed before: hearing, sight, flight, language. Whence this novelty? I was led to doubt that we could prestate the novelty. I came to doubt that we could finitely prestate all possible adaptations that might arise in a biosphere. In turn, I was led to doubt that we can prestate the «configuration space" of a biosphere.

But how strange a conclusion. In statistical mechanics, with its famous liter box of gas as an isolated thermodynamic system, we can prestate the configuration space of all possible positions and momenta of the gas particles in the box. Then Ludwig Boltzmann and Willard Gibbs taught us how to calculate macroscopic properties such as pressure and temperature as equilibrium averages over the configuration space. State the laws and the initial and boundary conditions, then cal-culate; Newton taught us how to do science this way. 

What if we cannot prestate the configuration space of a biosphere and calculate with Newton's "method of fluxions," the calculus, from initial and boundary conditions and laws? Whether we can calculate or not does not slow down the persistent evolution of novelty in the biosphere. But a biosphere is just another physical system. So what in the world is going on? Literally, what in the world is going on?

We have much to investigate. At the end, I think we will know more than at the outset. But Investigations is at best a mere beginning.

It is well to return to Schrödinger's brilliant insights and his attempt at a central definition of life as a well-grounded starting place. Schrödinger 's What Is Life? provided a surprising answer to his enquiry about the central character of life by posing a core question: What is the source of the astonishing order in organisms?

The standard—and Schrödinger argued, incorrect—answer, lay in statistical physics. If an ink drop is placed in still water in a petri dish, it will diffuse to a uni-form equilibrium distribution. That uniform distribution is an average over an enormous number of atoms or molecules and is not due to the behavior of indi-vidual molecoles. Any local fluctuations in ink concentration soon dissipate back to equilibrium.

Could statistical averaging be the source of order in organisms? Schrödinger based his argument on the emerging field of experimental genetics and the recent data on X-ray induction of heritable genetic mutations. Calculating the "target size" of such mutations, Schrödinger realized that a gene could comprise at most a few hundred or thousand atoms.

The sizes of statistical fluctuations familiar from statistical physics scale as the square root of the number of particles N. Consider tossing a fair coin 1o,ooo times. The result will be about 50 percent heads, 50 percent tails, with a fluctuation of about 1oo, which is the square root of 1o,ooo. Thus, a typical fluctuation from 50:50 heads and tails is 1oo/1o,ooo or 1 percent. Let the number of coin flips be 1oo million, then the fluctuations are its square root, or 1o,ooo. Dividing, 1o,ooo/1oo,ooo,ooo yields a typical deviation of .o1 percent from 50:50.

Schrödinger reached the correct conclusion: If genes are constituted by as few as several hundred atoms, the familiar statistical fluctuations predicted by statisti-cal mechanics would be so large that heritability would be essentially impossible. Spontaneous mutations would happen at a frequency vastly larger than observed. The source of order must lie elsewhere.

Quantum mechanics, argued Schrödinger, comes to the rescue of life. Quantum mechanics ensures that solids have rigidly ordered molecular structures. A crystal is the simplest case. But crystals are structurally dull. The atoms are arranged in a regular lattice in three dimensions. If you know the positions of all the atoms in a minimal-unit crystal, you know where all the other atoms are in the entire crystal. This overstates the case, for there can be complex defects, but the point is clear. Crystals have very regular structures, so the different parts of the crystal, in some sense, all "say" the same thing. As shown below, Schrödinger translated the idea of "saying» into the idea of "encoding." With that leap, a regular crystal cannot encode much "information." All the information is contained in the unit cell.

If solids have the order required but periodic solids such as crystals are too reg-ular, then Schrödinger puts his bet on aperiodic solids. The stuff of the gene, he bets, is some form of aperiodic crystal. The form of the aperiodicity will contain some kind of microscopic code that somehow controls the development of the or-ganism. The quantum character of the aperiodic solid will mean that small discrete changes, or mutations, will occur. Natural selection, operating on these small dis-crete changes, will select out favorable mutations, as Darwin hoped.

Fifty years later, I find Schrödinger's argument fascinating and brilliant. At once he envisioned what became, by 1953, the elucidation of the structure of DNA's ape-riodic double helix by James Watson and Francis Crick, with the famously under-stated comment in their original paper that its structure suggests its mode of replication and its mode of encoding genetic information. Fifty years later we know very much more. 

We know the human genome harbors some 80,ooo to 1oo,ooo "structural genes," each encoding the RNA that, after being transcribed from the DNA, is translated according to the genetic code to a linear sequence of amino acids, thereby constituting a protein. From Schrödinger to the establishment of the code required only about twenty years. 

Beyond the brilliance of the core of molecular genetics, we understand much concerning developmental biology. Humans have about 60 different cell types: liver, nerve, muscle. Each is a different pattern of  expression of the 80,000 or100,000 genes. Since the work of Francois Jacob and Jacques Monod thirty-five years ago, biologists have understood that the protein transcribed from one gene might turn other  genes on or off. Some vast network of regulatory interactions among genes and their products provides the mechanism that marshals the genome into the dance of development. 

We have come close to Schrödinger's dream. But have we come close to answer-ing his question, What is life? The answer almost surely is no. I am unable to say, all at once, why I believe this, but I can begin to hint at an explanation. Investigations is a search for an answer. I am not entirely convinced of what lies within this book;the material is too new and far too surprising to warrant conviction. Yet the pathways I have stumbled along, glimpsing what may be a terra nova, do seem to me to be worth serious presentation and serious consideration.

Quite to my astonishment, the story that will unfold here suggests a novel answer to the question, What is life? I had not expected even the outlines of an answer, and I am astonished because I have been led in such unexpected directions.

One direction suggests that an answer to this question may demand a fundamental alteration in how we have done science since Newton. Life is doing something far richer than we may have dreamed, literally something incalculable. What is the place of law if, as hinted above, the variables and configuration space cannot be prespecified for a biosphere, or perhaps a universe? Yet, I think, there are laws. And
if these musings be true, we must rethink science itself.

Perhaps I can point again at the outset to the central question of an autonomous agent. Consider a bacterium swimming upstream in a glucose gradient, its flagellar motor rotating. If we naively ask, «What is it doing?" we unhesitatingl answer something like, «It's going to get dinner." That is, without attributing con-sciousness or conscious purpose, we view the bacterium as acting on its own behalf in an environment. The bacterium is swimming upstream in order to obtain the glucose it needs. Presumably we have in mind something like the Darwinian criteria to unpack the phrase, "on its own behalf." Bacteria that do obtain glucose or ist equivalent may survive with higher probability than those incapable of the flagellar motor trick, hence, be selected by natural selection.

An autonomous agent is a physical system, such as a bacterium, that can act on its own behalf in an environment. All free-living cells and organisms are clearly au-tonomous agents. The quite familiar, utterly astonishing feature of autonomous agents—E. coli, paramecia, yeast cells, algae, sponges, flat worms, annelids, all of us —is that we do, everyday, manipulate the universe around us. We swim, scramble, twist, build, hide, snuffle, ponnce.

Yet the bacterium, the yeast cell, and we all are just physical systems. Physicists, biologists, and philosophers no longer look for a mysterious elan vital, some ethe-real vital force that animates matter. Which leads immediately to the central, and confusing, question: What must a physical system be such that it can act on its own behalf in an environment? What must a physical system be such that it constitutes an autonomous agent? I will leap ahead to state now my tentative answer: A mo-lecular autonomous agent is a self-reproducing molecular system able to carry out one or more thermodynamic work cydes.

All free-living cells are, by this definition, autonomous agents. To take a simple example, our bacterium with its flagellar motor rotating and swimming upstream for dinner is, in point of plain fact, a self-reproducing molecular system that is carrying out one or more thermodynamic work cycles. So is the paramecium chasing the bacterium, hoping for its own dinner. So is the dinoflagellate hunting the paramecium sneaking up on the bacterium. So are the flower and flatworm. So are you and I.

It will take a while to fully explore this definition. Unpacking its implications reveals much that I did not remotely anticipate. An early insight is that an autonomous agent must be displaced from thermodynamic equilibrium. Work cycles cannot occur at equilibrium. 

Thus, the concept of an agent is, inherently, a non-equilibrium concept. So too at the outset it is clear that this new concept of an au-tonomous agent is not contained in Schrödinger's answer. Schrödinger's brilliant leap to aperiodic solids encoding the organism that unleashed mid-twentieth-century biology appears to be but a glimmer of a far larger story.


....Ways of making a living, natural games, that are well searched out and well mas-tered by the evolutionary search strategies of organisms, namely, mutation and recombination, will be precisely the niches, or ways of making a living, that a diversifying and speciating population of organisms will manage to master. The ways of making a living presenting fitness landscapes that can be well searched by the procedures that organisms have in hand will be the very ways of making a living that readily come into existence. If there were a way of making a living that could not be well explored and exploited by organisms as they speciate, that way of making a living would not become populated. Good jobs, like successful jobholders, prosper.

So organisms, niches, and search procedures jointly and self-consistently co-construct one another! We make the world in which we make a living such that we can, and have, more or less mastered that evolving world as we make it. 

The same is true, I will argue, for an econosphere. A web of economic activities, firms, tasks, jobs, workers, skills, and learning, self-consistently came into existence in the last forty thousand years of human evolution.

The strange thing about the theory of evolution is that everyone thinks he un-derstands it. But we do not. A biosphere, or an econosphere, self-consistently co-constructs itself according to principles we do not yet fathom.

Laws for a Biosphere

But there must be principles. Think of the Magna Carta, that cultural enterprise founded on a green meadow in England when John I was confronted by his nobles. British common law has evolved by precedent and determinations to a tangled web of more-or-less wisdom. When a judge makes a new determination, sets a new precedent, ripples of new interpretation pass to near and occasionally far reaches of the law. Were it the case that every new precedent altered the interpretation of al1 old judgments, the common law could not have coevolved into its rich tapestry. Conversely, if new precedents never sent out ripples, the common law could hardly evolve at all.

There must be principles of coevolutionary assembly for biospheres, economic systems, legal systems. Coevolutionary assembly must involve coevolving organi-zations flexible enough to change but firm enongh to resist change. Edmund Burke was basically right. Might there be something deep here? Some hint of a law of co-evolutionary assembly?

Perhaps. I begin with the simple example offered by Per Bak and his colleagues some years ago—Bak's "sand pile» and "self-organized criticality." The experiment requires a table and some sand. Drop the sand slowly on the table. The sand grad-ually piles up, fills the tabletop, piles to the rest angle of sand, then sand avalanches begin to fall to the floor.

Keep adding sand slowly to the sand pile and plot the size distribution of sand avalanches. You will obtain many small avalanches and progressively fewer large E avalanches. In fact, you will achieve a characteristic size distribution called a «power law." Power law distributions are easily seen if one plots the logarithm of the number of avalanches at a given size on they-axis, and the logarithm of the size of the avelanche on the x-axis. In the sand pile case, a straight line sloping down-ward to the right is obtained. The slope is the power law relation between the size and number of avalanches.

Bak and his friends called their sand pile "self-organized critical." Here, «criti-cal" means that avalanches occur on all length scales, "self-organized" means that the system tunes itself to this critical state.

Many of us have now explored the application of Bak's ideas in models of co-evolution that I will discuss shortly. With caveats that other explanations may ac-count for the data, the general result is that something may occur that is like a theory of coevolutionary assembly that yields a self-organized critical biosphere with a power law distribution of small and large avalanches of extinction and speciation events. As we shall see, the best data now suggest that precisely such a power law distribution of extinction and speciation events has occurred over the past 6So million years of the Phanerozoic. In addition, the same body of theory predicts that most species go extinct soon after their formation, while some live a long time. The predicted species lifetime distribution is a power law. So too are the data.

Similar phenomena may occur in an econosphere. Small and large avalanches of extinction and speciation events occur in our technologies. A colleague, Brian Arthur, is fond of pointing out that when the car came in, the horse, buggy, buggy whip, saddlery, smithy, and Pony Express went out of business. The car paved the way for an oil and gas industry, paved roads, motels, fast-food restaurants, and suburbia. The Austrian economist Joseph Schumpeter wrote about this kind of turbolence in capitalist economies. These Schumpeterian gales of creative destruc-tion appear to occur in small and large avalanches. Perhaps the avalanches arise in power laws. And, like species, most firms die young; some make it to old age— Storre, in Sweden, is over nine hundred years old. The distribution of firm lifetimes is again a power law.

Here are hints—common law, ecosystems, economic systems—that general principles govern the coevolutionary coconstruction of lives and livings, organ-isms and natural games, firms and economic opportunities. Perhaps such a law governs any biosphere anywhere in the cosmos.

I shall suggest other candidate laws for any biosphere in the course of Investigations. As autonomous agents coconstruct a biosphere, each must manage to categorize and act upon its world in its own behal£ What principles might gov-ern that categorization and action, one might begin to wonder. I suspect that au-tonomous agents coevolve such that each makes the maximum diversity of reliable discriminations upon which it can act reliably as it swims, scrambles, pokes, twists,

and pounces. This simple view leads to a working hypothesis: Communities of agents will coevolve to an "edge of chaos" between overrigid and overfluid behav-ior. The working hypothesis is richly testable today using, for example, microbial communities.

Moreover, autonomous agents forever push their way into novelty—molecular, morphological, behavioral, organizational. I will formalize this push into novelty as the mathematical concept of an "adjacent possible," persistently explored in a universe that can never, in the vastly many lifetimes of the universe, have made all possib}e protein sequences even once, bacterial species even once, or legal systems even once. Our universe is vastly nonrepeating; or, as the physicists say, the uni-verse is vastly nonergodic. Perhaps there are laws that govern this nonergodic flow. I will suggest that a biosphere gates its way into the adjacent possible at just that rate at which its inhabitants can just manage to make a living, just poised so that selection sifts out useless variations slightly faster than those variations arise. We ourselves, in our biosphere, econosphere, and technosphere, gate our rate of dis-covery. There may be hints here too of a general law for any biosphere, a hoped-for new law for self-constructing systems of autonomous agents. Biospheres, on aver-age, may enter their adjacent possible as rapidly as they can sustain; so too may econospheres. Then the hoped-for fourth law of thermodynamics for such self-constructing systems will be that they tend to maximize their dimensionality, the number of types of events that can happen next.

And astonishingly, we need stories. If, as I will suggest, we cannot prestate the configuration space, variables, laws, initial and boundary conditions of a biosphere, if we cannot foretell a biosphere, we can, nevertheless, tell the stories as it unfolds. Biospheres demand their Shakespeares as well as their Newtons. We will have to rethink what science is itsel£ And C. P. Snow's "two cultures," the humanities and science may find an unexpected, inevitable union.

Investigations leads us to new views of the biosphere as a coconstructing system. In the final chapter, I step beyond the central concern with autonomous agents to consider the universe itself. Again, there are hints of coconstruction—of the laws themselves, of the complexity of the universe, of geometry itself.The epilogue con-dudes with limits to reductionism in its strong form and an invocation to a constructivist science.