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The Origin of Life

A case is made for the descent of electrons

James Trefil, Harold J. Morowitz, Eric Smith

Selection Begins

We note that there is a fundamental difference between the way chemical reaction systems could have operated before the appearance of the first self-replicating molecules and the way they operate now that self-replicating systems have developed. In the beginning, the only potential source of order would have been networks of chemical reactions operating according to the laws of chemistry and physics. After molecules appeared that could replicate more or less independently, such as RNA, however, evolution could have proceeded according to the rules of natural selection, with the success of subsequent generations dependent on adaptive properties. Exactly when and how this transition occurred remains an open question debated by researchers, but the fact that it did occur is plain. Another way of saying this is that before the appearance of the first self-replicating molecules or assemblages of molecules (and, again, we have to emphasize that these may or may not have been inside cells), what mattered was the persistence of the chemical network; after such a system appeared, natural selection took on its more familiar form of selection among rival reproducing “individuals.”

Once natural selection began, systems with slightly different chemistry would appear on the scene through random accident. For example, acetate can be used in two ways to make oily molecules, and the major domains of life divide, in part, according to which class they make and how they use them. Methane production purely for energetic purposes may have been primordial, or it may have been coupled to metabolism in a later, more complicated age (another topic of serious debate among researchers investigating the deepest branches of the tree of life).

The important pattern to appreciate is that the primordial cycle provides the stability and starting materials that make an age of selection possible. We think it was at the transition to this stage that geochemistry began to take on the features of replication and selection recognized by Darwin as distinctive of life. After such an age has begun, it can maintain the complexity and diversity needed to explore for refinements—in efficiency, in adaptation to the geological environment or in specialized division of labor within communal systems. The same pattern repeated itself when the environment was changed by the accumulation of a destructive toxin—oxygen—that was produced by primordial organisms as a waste product. As they adapted, organisms did not abandon the reductive citric acid cycle, which we believe was the unique foundation for biosynthesis. Instead they acquired the ability to run the cycle in reverse, extracting energy from the breakdown of molecules similar to those the cycle formerly produced.

The role of the citric acid cycle as a foundation for complexity applies not only to subsequent adaptation by organisms under selection; it can be seen even within the chemical structure of the metabolic core itself. A particularly powerful way to make this point is to rework the schematic chart of current metabolism first developed by Nicholson. The original Nicholson chart was developed to elaborate human metabolism and was gradually expanded to incorporate the complex webs of chemistry on which humans depend. Recently, one of us (Morowitz) and Vijay Srinivasan used evidence from microbiology to distill the Nicholson chart, with its complex modules and domains of metabolism, down to a minimal common core, the necessary and sufficient network of reactions to make a living system. Within this core chart, which will be published soon, we arrayed pathways as layers built around citric acid cycle precursors. A fragment of that detailed chart is shown in Figure 4. The innermost layer consists of molecules that can be built from cycle intermediates with one chemical reaction, the next layer consists of those that can be built with two reactions, and so on. (Once you get past the first few layers, the counting becomes ambiguous, as the reactions often involve molecules that were themselves the products of layers farther in).

From this layered structure we believe we can see the chemical cascade that comprised the earliest steps in the evolution of life.

Figure 4. Metabolism of chemoautotrophsClick to Enlarge ImageThe primordial core chart is simpler than the elaborate chart made by combining organisms today, but it is not much simpler biosynthetically. It contains the major modules for sugars, oils and amino and nucleic acids, and we have proposed that it was—at least in broad outline—the agency of chemical selection in an era that preceded natural selection on distinguishable organisms.

If this notion turns out to be true, it will have important implications for a deep philosophical question: whether we should understand the history of life in terms of the working out of predictable physical principles or of the agency of chance. We are, in fact, arguing that life will appear on any planet that reproduces the environmental and geological conditions that appeared on the early Earth, and that it will appear in order to solve precisely the sort of ”stranded electron” problem discussed above. The currently popular view that complex life was something of a frozen accident was set forth in Jacques Monod’s classic book Chance and Necessity (1970). We, of course, are arguing the opposite, if only for a significant part of basic chemical architecture. (It is important to appreciate that Monod studied regulatory systems, and in the domain of his expertise, we recognize the importance of accident, though we believe he advocated it too broadly.) It has not escaped our notice that the mechanism we are postulating immediately suggests that life is widespread in the universe, and can be expected to develop on any planet whose chemistry resembles that of the early Earth.

The view of life originating as a network of simple chemical reactions will require a lot of testing before it is adopted by the scientific community. We identify two areas where research is being pursued: the development of the theory of nonequilibrium statistical mechanics and the experimental pursuit of those first nonenzymatic chemical reactions that led to modern life.

On the theoretical side, we have to start with the realization that if we apply standard equilibrium thermodynamics to living systems, we arrive at something of a paradox. Living systems possess low entropy, which makes them very improbable from the equilibrium thermodynamic viewpoint. From the point of view of theoretical physics, the basic problem is that classical thermodynamics has only been well developed for systems in equilibrium—systems that do not change over time—or that change only by moving through successive, infinitesimally different equilibrium states. What is needed, therefore, is an extension of ordinary thermodynamics so that it can apply to systems maintained far from equilibrium by the flow of energy.

One promising approach was first suggested by E. T. Jaynes in the mid-20th century. He recognized that information (and hence entropy) is associated not just with states but with whole histories of change, which can include channel flows of the sort we have been discussing. Technically, one cannot talk about the entropy “of a state” if the state depends for its context on a process of change; only the entropy of the whole process is expected to be maximized. To return to our pond on the hill, there is not a separate entropy of the pond, except as an approximation. Rather, there is an entropy of paths of change that include pond, channel, construction and relaxation. When such a formulation is analyzed for a simple system, the establishment of a channel can be seen as a phase transition, similar to the freezing of an ice cube or, to use a more precise mathematical analogy, the formation of a magnet from molten iron. (In the latter case, the phase transition occurs as the metal cools when the atomic dipole magnets line up in the same direction—paradoxically, a more ordered state). The full entropy of the process will be maximized in the system, even though the approximate entropy associated with the “state” of the channel may not be, thereby eliminating the paradox.

Current research into this foundational question now centers on the fact that the chemical substrate of living systems is much more complex than that of simple physical systems that have been examined so far. One important new direction of research involves the development of small-molecule catalysts in increasingly complex cooperative networks. The hope is that when a full theory is available, we will see the formation of life as an inevitable outcome of basic thermodynamics, like the freezing of ice cubes or the formation of magnets.

Figure 5. Sagittarius B2(N)Click to Enlarge ImageOn the experimental side, some researchers, such as George Cody at the Carnegie Institution of Washington, D.C., are trying to work out the basic rules of organic chemistry for exotic environments that might have been relevant to the origin of life. Cody, for example, has worked on unraveling organic interactions at the kinds of temperatures and pressures that obtain at deep ocean vents. Mike Russell at the Jet Propulsion Laboratory in Pasadena, California, (author of “First Life,” January–February 2006) is building a large chamber to model the geochemistry of those environments. Shelley Copley at the University of Colorado at Boulder has been sorting out the intermediate chemistry leading to the current nucleic acid–protein system of genetic coding, with an eye toward resolving the chicken-and-egg problem. These experiments represent a major paradigm shift from the top-down control envisioned in RNA World scenarios. Rather than supposing that a few large RNA molecules control the adaptation of a passive small-molecule reaction network, Copley supposes that whole networks of intermediate molecules support each other on the path toward complexity. In this experimental setting, networks of small and randomly synthesized amino acids and single RNA units aid each others’ formation, assembly into strings and evolution of catalytic capacity. Both types of molecules grow long together. Complexity, adaptation and control are distributed in such networks, rather than concentrated in one molecular species or reaction type. Distributed control is likely to be a central paradigm in the development of Metabolism First as a viable theory. We eagerly anticipate more experimental efforts like these to explore the many facets of small-molecule system organization.

In a larger sense, however, the future of the experimental program associated with the Metabolism First philosophy is tied to the development of the appropriate theory, guided by experimental results. The hope is that the interplay of theory and experiment, so familiar to historians of science, will produce a theory that illuminates the physical principles that led to the development of life and, hence, give us the ability to re-create life in our laboratories.

Assuming the experimental and theoretical programs outlined above work out well, our picture of life as a robust, inevitable outcome of certain geochemical processes will be on firm footing. Who knows? Maybe then someone will write a book titled Necessity, Not Chance.


  • Morowitz, H. J. 1999. A theory of biochemical organization, metabolic pathways, and evolution. Complexity 4:39–53
  • Smith, E., and H. J. Morowitz. 2004. Universality in intermediary metabolism. Proceedings of the National Academy of Sciences of the U.S.A. 101:13168–13173.
  • Morowitz, H. J., and E. Smith. 2007. Energy flow and the organization of life. Complexity 13:51–59.
  • Srinivasan, V., and H. J. Morowitz. 2009. The canonical network of autotrophic intermediary metabolism. Biological Bulletin. In Press.

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