The Origin of Life
A case is made for the descent of electrons
A Pair of Analogies
Sidebar: Metabolism 101
Here’s an analogy that will provide an outline for the argument we make: Consider the requirements of the U.S. Interstate highway system. The system includes an enormously complex network of roads; major infrastructure devoted to extracting oil from the Earth, refining oil into gasoline and distributing gasoline along the highways, a major industry devoted to producing automobiles; and so on. If we wanted to explain this system in all of its complexity, we would not ask whether cars led to roads or roads led to cars, nor would we suspect that the entire system had been created from scratch as a giant public works project. It would be more productive to consider the state of transport in preindustrial America and ask how the primitive foot trails that must certainly have existed had developed into wagon roads, then paved roads and so on. By following this evolutionary line of argument, we would eventually account for the present system in all its complexity without needing recourse to highly improbable chance events.
In the same way, we argue, the current complexity of life should be understood as the result of a multistep process, beginning with the catalytic chemistry of small molecules acting in simple networks—networks still preserved in the depths of metabolism—elaborating these reaction sequences through processes of simple chemical selection, and only later taking on the aspects of cellularization and organismal individuality that make possible the Darwinian selection that biologists see today. Our task as origin-of-life researchers is to look at the modern highways and see what they reveal about the original foot trails.
The very robustness of modern life makes such questions difficult, because the metabolism that we see today seems to be one on which life has converged, and around which it reorganizes after historical shocks such as the oxygenation of the atmosphere at the beginning of the paleoproterozoic era, the emergence of multicellularity, dramatic climate changes that have reshaped environments and so on. To avoid confusing this convergent form with one toward which evolution was “directed,” we focus instead on the nonliving world that preceded life and ask “what was wrong” with such a world, which created the first steps toward life as a departure. In other words, what was the “problem” that a lifeless earth “solved” by the emergence of life?
Another analogy will illustrate how this question should be understood. Imagine a large pond of water sitting on top of a hill. We know that there are any number of other states—any in which the water is lower than it is at the top—which have lower energy and are therefore states toward which the system will tend to evolve over time. In terms of our question, the ”problem” faced by the system is how to get water from its initial state to any state of lower energy—how to get the water down the hill. We need not think of the laws of physics as being endpoint directed; rather, they simply adjudicate between states of higher or lower energy, with a preference for lower. Can we apply the same reasoning to the chemistry of life?
For real hills, we understand not only that the water will flow downward but also many things about how it will do so. Molecules of water will not each flow down a random path. Instead the flowing water will cut a channel in the hillside. In fact, the flow of water is at once constructing a channel and contributing to the collapse of the energy imbalance that drives the entire process. In addition, if we look at this process in detail, we see that what really matters is the configuration of the earth near the top of the hill, for it is there that the channeling process starts. This part of the analogy turns out to be particularly appropriate when we consider early chemical reactions.
In the analogy, the “problem” is the fact that the water begins in a state of high energy; the creation of the channel ”solves” this problem by allowing the water to move to a lower energy state. Furthermore, the dynamics of the system are such that once the channel is established, subsequent flow will reinforce and strengthen it. There are many such systems of channels in nature—the lightning bolt is an example, although in that case the forces at work are electrical, not gravitational. (When lightning occurs, positive and negative charges become separated between clouds and the ground. The charge separation ionizes atoms in the air, creating a conducting channel through which the charges flow—the lightning bolt—much as water flows down a hill).
We argue that the appearance of life on our planet followed the creation of just such a channel, except that it was a channel in a chemical rather than a geological landscape. In the abiotic world of the early Earth, likely in a chemically excited environment, reservoirs of energy accumulated. In effect, electrons (along with certain key ions) were pumped up chemical hills. Like the water in our analogy, those electrons possessed stored energy. The “problem” was how to release it. In the words of Albert Szent-Gyorgi: “Life is nothing but an electron looking for a place to rest.”
For example, carbon dioxide and hydrogen molecules are produced copiously in ordinary geochemical environments such as deep sea vents, creating a situation analogous to the water on the hill. The energy of this system can be lowered if the electrons in the hydrogen ”roll down the hill” by combining with the atoms of carbon dioxide in a chemical reaction that produces water and acetate (a molecule with two carbon atoms). In the abiotic world, however, this particular reaction takes place so slowly that the electrons in the hydrogen molecles find themselves effectively stranded at the top of the energy hill.
In this example, the problem that is solved by the presence of life is getting energized electrons back down the chemical hill. This is accomplished by the establishment of a sequence of biochemical channels, each contributing to the whole. (Think of the water cutting multiple channels in the hill). The reactions that create those channels would involve simple chemical transactions between small organic molecules.
How can we translate these sorts of general arguments into a reasonable scenario for the appearance of the first living thing? One way would be to look closely at the metabolic chart shown earlier, the diagram that maps the basic chemical reactions in all living systems.
At the very core of metabolism—the starting point for the synthetic pathways of all biomolecules—is a relatively simple set of reactions known as the citric acid cycle (also called the tricarboxylic acid cycle or the Krebs cycle). The cycle involves eight molecules, each a carboxylic acid (a molecule containing —COO groups). In most present-day life forms on Earth, the citric acid cycle operates to break organic molecules down into carbon dioxide and water, using oxygen to produce energy for the cell—in effect, ”burning” those molecules as fuel. (Technically, a molecule like glucose is first broken down into smaller molecules like pyruvate, which is then fed into the citric acid cycle. Full decomposition of pyruvate to CO2 and water is facilitated by transfer of high-energy electrons to certain coreactants that, in the modern cell, ferry the electrons to other reactions). When the cycle operates in this way, we say that it is in its oxidative mode.
The cycle can also operate in the opposite direction, taking in energy (in the form of high-energy electrons) and building up larger molecules from smaller ones. This is called the reductive mode of the cycle. If an organism has access to high-energy electrons like those produced by geochemical processes, in fact, it can thrive with the cycle exclusively in the reductive mode, having no use for the oxidative mode at all. One way to think about the two modes of the cycle is this: In the oxidative mode, the input is an organic molecule, and the output is chemical energy, carbon dioxide and water. In the reductive mode, the input is chemical energy, carbon dioxide and water, and the output is a more complex molecule.
This must have been the way the cycle operated on the early Earth, because molecular oxygen was not available primordially to support the oxidative mode, and because we see it operating this way today in some anaerobic organisms that seem to have preserved this aspect of the biochemistry of their ancestors. In the reductive mode, the cycle provides a way for high-energy electrons to flow down the chemical hill. It is similar to the acetate reaction shown earlier, which is thermodynamically feasible but very slow, but with the addition of a network of small molecules—the reductive citric acid cycle—acting to mediate and speed up the reaction. On biochemical and thermodynamic grounds, then, the reductive citric acid cycle (or some simpler precursor) would be a good candidate for the threshold of early life—the point where the pond of high-potential water is breached and the downhill pathway is etched out. The slow uncatalyzed conversion of carbon dioxide and hydrogen into acetate and water, shown earlier, occurs efficiently as the energy and reactants enter a primordial network of reactions like the modern-day reductive citric acid cycle.
In the metabolic maps of all modern organisms, the small molecules and reactions of the citric acid cycle are the starting point of every biosynthetic pathway—all roads lead from the citric acid cycle. However, in some organisms the reactions do not form a closed—cyclic—reaction sequence. For that reason, even among researchers convinced that these reactions are vestiges of the first metabolism, debate remains over whether the very first metabolic footpath was a cycle. However, because only cycles can act as self-amplifying channels, and because in organisms not running the closed cycle, sophisticated compensating adaptations are required, we consider a primordial reductive citric acid cycle the most likely route from geochemistry to life—the rivulet that formed at the top of the energy hill, through which the pond of energy began its thermodynamic escape. We then ask how, from this simple beginning, could the complexity we see in the modern cell arise. The first thing to notice is that, taken by itself, the cycle captures only part of the energy in the carbon dioxide and hydrogen that constitute its input. In transforming the carbon dioxide to acetate, for example, the cycle harvests only about a third of the energy available in the electrons. Even in the deep core of metabolism, however, we do not see the cycle in isolation. Its lowest-energy molecule, acetate, is the starting point for other pathways that make the essential oils used in cell membranes, harvesting another third of the electron energy. Further reactions, such as those that generate methane, can capture the remaining available energy, though methane is a gas and therefore a waste product, unlike the earlier molecules in the pathway, which are constituents of biomass.