The Equations of Life

by Charles S. Cockell

  The molecule so produced, ATP, can be transported around the cell, and its phosphate groups can be broken off to release their energy anywhere it is needed, for making new proteins, repairing old ones, and eventually making new cells. If you think this is a trifling process, your body, in all its cells, produces about 1.4 × 1021 molecules of ATP per second! It has cost you about 2.5 × 1024 ion molecules of ATP just to read this chapter.

  Ponder this whole process. There is certainly complexity in all this: different molecules for collecting electrons, the machinery for making ATP, and even the ATP itself, which is a small molecule, but one that nevertheless has a subtlety and intricacy in how phosphate bonds are used to trap energy.

  However, at the core of this process is an incredible simplicity. Here we have readily accessible subatomic particles, electrons, with some energy to give away being used to produce a gradient of another subatomic particle, protons. This gradient is then employed, by the rather basic principle of osmosis, to do work in rotating a miniature machine that produces a molecule that effectively stores that energy for release anywhere it is useful. This is a mechanism of alluring modesty.

  I have heard it said that this system of gathering energy is highly idiosyncratic. With the benefit of hindsight, it looks simple. However, would life elsewhere really use such a system? To put the question slightly differently, give an engineer a pad of paper and a pen, and ask them to devise a system for harvesting energy from the environment. Would they come up with the same thing?

  For the unconvinced, I would merely observe that engineers have done almost the same thing. Hydroelectric power, used in over 150 countries around the world, is made by damming water high in a lake and then allowing it to flow down a mountainside, using the kinetic energy of the water as it rushes down a hill to create rotary motion in a turbine that generates electricity. The details are different in the cell, but the basic idea is the same. Life pumps protons into a reservoir outside a membrane. The membrane acts as a dam to trap the protons outside. Then it uses the gradient of osmosis to produce rotary motion in the ATP synthase as those protons rush back through our molecular turbine. Rather than producing electricity, the minuscule turbine is instead used to store energy in ATP. However, even ATP is analogous to the storage of electric power in batteries for use at a later time or place. In the cell, we do not have hydroelectric power, but we have proton electric power.

  Let us imagine the implausible scenario that the field of biochemistry was never developed, but that for some obscure reason, we knew that cells have impermeable membranes. Now give an engineer a pad of paper and a pen, and ask them to devise a system of gathering energy from atoms. I see no reason why they would not, by thinking about hydroelectric power stations, conceive of a system in which electrons were used to make some sort of gradient of ions with microscopic pumps. That gradient would itself be used to channel those ions back into a cell through a rotary device to make electricity or chemical compounds that contain energy.

  The chemiosmosis theorem, Mitchell’s brainchild, has a certain logic to it, but one might still ask, why the proton gradient? Each movement of an electron from one protein to another releases a tiny amount of energy. We want to gather it all up. Making a gradient by pumping protons is clever because each transfer of an electron contributes to a proton gradient outside the membrane, and the gradient is the accumulated product of many of these electron movements. We end up with a relatively large accumulation of protons, like our water in a mountaintop reservoir. These collected protons can now be channeled through a single machine to capture the energy.

  The quintessential question that we might ask again is whether there is any room for chance and contingency in all this, any room for serendipitous attributes of historical quirks. Or is the architecture of this process locked into an unyielding pattern?

  We already know that within this energy-making machinery, there is room for flexibility in the detail. Some microbes can use sodium ions (Na+) instead of protons to generate their gradient. In an ingenious study, a group from Germany used chemicals that punch holes in the membranes of bacteria to show that when the membranes had holes that would allow protons to uncontrollably leak into the bacterium Acetobacterium woodii, the organism’s ability to use the chemical caffeate in its electron transport chain was unaffected. However, when the holes in the membrane allowed sodium ions to leak through, the organism’s ability to make ATP was destroyed. Here is a microbe that has eschewed protons for sodium ions, a microbe that illustrates the possibility of modifications to this ingenious apparatus. Nevertheless, protons are the most common way to make a gradient across the membrane for all the major domains of life, and the use of proton gradients may be no coincidence, but rather deeply embedded in the origin of life itself.

  This machinery for extracting energy has an even more remarkable versatility to it. And this is where things turn extraordinary.

  Life does not necessarily need sandwiches and oxygen. We can use different electron donors and acceptors and make a life form that can grow using a whole variety of other things to be found lying around in the universe. You and I need oxygen to breathe, but oxygen is not the only chemical that can carry off electrons from the cell. Many microbes instead use iron or sulfur compounds that, like oxygen, seize electrons. The result of this switch is the anaerobes, microbes that can live without oxygen. Deep underground or in a muddy, fetid pool, these microbes go about their lives without a hint of the gas, growing in rocks, in bogs, or deep in the sulfurous pools of volcanoes. These are creatures breathing bounteous elements such as iron, sulfur, and their respective compounds. This simple swap of electron acceptors opens up a new landscape of habitats and environments for life where humans cannot go.

  The potential for life does not end there. Not only can we forsake oxygen for another electron acceptor, but we may also select other electron donors—away with sandwiches! Swap them for hydrogen, and we now have a microbe that can instead use hydrogen gas from deep underground as a source of food. These so-called chemolithotrophs, literally, chemical rock eaters, have many advantages over us. Freed of the need for organic matter, they can now live a life essentially independent of the rest of the biosphere, even underground in the absence of light.

  The limitation of using organic matter, including the sandwiches, as a food source is that its components come from other microbes, plants, and animals. This interdependency between different types of life is the basis of food webs that make up much of the ecology of our planet; herbivores eat plants and carnivores eat the herbivores and other carnivores, nothing more than a complex web of electrons moving around from one life form to another. However, by feeding off hydrogen, microbes are feasting on the raw materials of planets. No group of people is more fascinated by the chemolithotrophs than are astrobiologists, as they wonder whether these metabolisms would allow life to live deep underground in habitable regions of other planets.

  By mixing and matching electron donors and acceptors, we can make energy from a wide range of chemicals on offer. The methanogens, microbes that make methane gas, use hydrogen gas as their electron donor and carbon dioxide gas as the electron acceptor. Hydrogen gas can be ancient, trapped in a planet during the planet’s formation, or the gas is produced when certain minerals react with water in the process of serpentinization. Creeping through rock fractures, dissolved in water, hydrogen can drive whole ecosystems. Microbial communities that use hydrogen as their main source of electron donors inhabit many of the boiling volcanic pools in Yellowstone National Park, the hydrogen produced deep underground in the magma-heated depths of this dormant supervolcano.

  The carbon dioxide that methanogens use to carry off those spent electrons is in no short supply, either. At a tiny fraction of the atmospheric composition, about 400 parts per million, the gas is still abundant enough to be used by the microbes as an electron acceptor, although it can be even more concentrated deep in the Earth.

  The methanogens spark the enthusiasm
of astrobiologists. Methane has been detected on Mars and in the plumes of Enceladus, one of Saturn’s moons. Is it the by-product of life? Well, there are ways in which methane can be produced without living things, so the mere presence of the gas is not an unequivocal sign of life. Methane can be made deep underground where gases react at high temperatures, and it can be trapped at low temperatures in ices, so-called clathrates, later to be released if the ices are warmed by volcanic activity. Nevertheless, the very controversy about the origins of methane drives astrobiology missions to find out whether its presence on other planets could be a sign of biology. Behind this quest to test the hypothesis that these faraway places host extraterrestrial life, the motivating driver for all this research is our knowledge of the amazing capabilities of the energy-producing machinery of life and the possibilities it hails.

  The electron transport chain is like a sort of modular energy system. The core molecules involved are very similar across different forms of life, built up from cytochromes, other proteins, and quinones that contain within them arrangements of iron and sulfur atoms particularly good at transporting electrons. At each end of the chain are the molecules that trap different electron donors and acceptors depending on where a creature lives and what is available to eat. Cells are by no means limited to one choice, either. They can bolt on new electron donors or acceptors depending on what is available around them. Like a hungry diner in a buffet switching to pasta when the pizza has run out, microbes can shift from iron to sulfur compounds and back again as the available energy sources change, giving them incredible versatility in the places they can subsist.

  One most astounding discovery of recent years is that microbes can even use free electrons, isolated electrons not associated with anything. Place an electrode into the sediment, and microbes will attach to the electrode, extracting the electrons directly from it to power their electron chains. A surprising number of microbes—Halomonas, Marinobacter, and others—have this ability. While the discovery that microbes can use electrons directly to make energy seems extraordinary, it perhaps should not surprise us. Many compounds I have been talking about, including those in your sandwiches, are merely containers for electrons. When free electrons are available, why not cut out the intermediary and take them directly?

  The consequences of the energetic versatility of these electron transfer chains cannot be underestimated. Each year, about 160 million tons of nitrogen gas from the atmosphere are taken up by so-called nitrogen-fixing bacteria and turned into ammonia, nitrites, and nitrates, more biologically available forms of nitrogen that feed the rest of the biosphere. Microbes that use these nitrogen compounds in electron transport chains to gather energy carry out all these transformations of nitrogen, from ammonia to nitrites and nitrates and back out again to the atmosphere as nitrogen gas.

  The same too with sulfur compounds. Elemental sulfur, thiosulfates, sulfates, and sulfides are all shunted around between different microbes and transformed back and forth, one into another, in global biogeochemical cycles that churn and turn elements and compounds through the Earth’s crust, providing them to the rest of life, including you and me.

  Probably one of the most interesting and profound discoveries in biology over the past few decades—a consequence of our insight into life’s energy-extracting machine—is that almost every electron donor-acceptor pair that theoretically might provide some energy for life has been found in nature. Any combination of two elements or compounds for which it is thermodynamically favorable for an electron to move from one entity to the other and give off energy is fair game.

  In a now seminal paper published in 1977, Engelbert Broda, an Austrian theoretical chemist, using some simple energetic and thermodynamic intuition, predicted the existence of microbes in the wild that hitherto had not been discovered. One of them was a bacterium that would use ammonia as the electron donor and nitrite as the electron acceptor. This anaerobic ammonia oxidation or anammox bacterium, as it was eventually called, was finally found in the 1990s. The process it drives turns out to be enormously important in the marine environment, accounting for about 50 percent of all the nitrogen gas produced in the oceans.

  Here we have an example of how knowing about the physics of life allowed for a prediction of a life form subsequently discovered. The view that physics is underpinned by laws that allow predictions and that biology is so varied that it lacks the predictive rigor of physics falls away. We see in the energetics of life simple thermodynamics embedded within the molecular machines of energy production. These basic principles allow us to predict the energy-gathering capacities of living things equally as well as apparently more simple energetic systems.

  Some of the energy gathering that microbes carry out has found very practical application in some surprising places. Instead of using oxygen as an electron acceptor, some microbes can use uranium, perhaps to be found in a contaminated nuclear waste site. The microbes, by using uranium in their electron pathways, alter the chemical state of the element. This new form of the element is less easily dissolved in water and is consequently less likely to leach its way into the water supply. Using microbes to change the state of hazardous chemicals in the environment into forms less likely to cause harm or be a public health risk is the ingenious process of bioremediation. Microbial energy gathering has now gone beyond pure academic knowledge and entered into the service of humanity in solving some of our emerging and urgent environmental problems.

  Before we lose sight of our purpose, I want to return to what all this means for evolution, for life and its possibilities.

  Combining sandwiches with oxygen produces a lot more energy, typically about ten times more, than do many reactions that use chemicals like iron or sulfur. Anaerobic lifestyles are quite energy poor and the microbes feeding off iron in the rocks or chomping on hydrogen deep underground are living life on the edge, the thermodynamic edge. If you want to run a brain (which in humans requires about twenty-five watts), run, jump, fly, and operate a body with many trillions of cells, you need a lot of energy. Those energy-yielding reactions that happen without oxygen are generally just too feeble to be used by most animals. In anaerobic habitats, life is limited by energy, yet another boundary set by physical processes.

  It is apparently no coincidence, then, that animal life on Earth emerged when oxygen levels in the Earth’s atmosphere increased to approximately 10 percent, the threshold at which the energy from aerobic respiration may have supported much more complex life. Aerobic respiration could have occurred at lower concentrations of oxygen than this, but life would have been denied the large-scale complexity we associate with animals. It took a revolution in energy acquisition to allow for the emergence of the biosphere with which we are all familiar.

  However, why did the concentrations of oxygen in the Earth’s atmosphere rise to allow for this dramatic increase in energy availability? We know that the oxygen gas in the Earth’s atmosphere came from photosynthesis. Cyanobacteria, pervasive green microbes that occupy the oceans, lakes, and rivers, figured out how to make energy from sunlight by splitting water molecules to release their electrons. Sunlight is used to energize the electrons that eventually end up running through our trusty electron transport chains to produce ATP. The splitting of water molecules for energy was a revolution because until then, life that used sunlight as a source of energy was confined to using chemicals like hydrogen and iron as their source of electrons. By switching to water, a most abundant and widespread resource, the oxygen-producing photosynthesizers conquered the Earth’s landmasses and waterways, presaging a huge production of oxygen gas.

  Unfortunately, the newly available oxygen was not immediately free to build up in the atmosphere. Because copious quantities of gases such as methane and hydrogen like to react with oxygen, the concentration of these other gases had to be lowered before the concentration of oxygen could rise. The chemical evidence locked in ancient rocks suggests that this increase in oxygen happened about 2.4 billion years ago in the
Great Oxidation Event and again about 750 million years ago; the second increase produced concentrations high enough to allow for animals. There has been no event of greater consequence for life than the rise of oxygen. This chemical change in the atmosphere is thought to be linked not only to the rise of animal life but also, by implication, to the rise of intelligence.

  So animals need oxygen, the electron acceptor that releases enough energy for a monkey to swing and jump through the rain forest, a dog to run and roll in the Meadows, and a human brain to think. But is there really no other way that animal life, let alone intelligence, could gather enough energy to evolve on a planet?

  At the end of the astrobiology course I teach at the University of Edinburgh, I finish with a lecture designed as much to educate as to entertain my long-suffering students. I walk into the lecture theater, announce that I am off to get a coffee and that the students will soon be greeted by a visiting lecturer. I return dressed in a full-body lizard-man outfit and face mask to deliver my lecture “Is there life on Naknar 3?”

  The lecture begins with a description of a distant extrasolar planet we have discovered. It is large, has oxygen in the atmosphere, and apparently has a moon. It becomes rapidly apparent to the students that the planet of which the visitor speaks is the Earth. The lecture weaves an internally self-consistent story about why this distant planet could not possibly support life. Throughout my discourse, I am forced to break off the lecture to munch on some sugar cubes, which the audience soon discovers is a supply of gypsum, or calcium sulfate. You see, I am a sulfate-reducing anaerobic alien that eats organic carbon, but instead of burning this in oxygen, I use sulfate as the electron acceptor. As this mode of energy production yields about ten times less energy than does aerobic respiration, I must constantly interrupt the lecture to snack.

  The high concentrations of oxygen on distant Naknar 3 make life unlikely there because living matter would combust in this gas. And besides, oxygen produces dangerous free radicals very damaging to carbon-based chemistry. To add to our meager assessment of this world, an additional theory is that the surface of this planet is made up of giant sheets of rock that move around, destroying the ancient sulfate mounds that provide food for life and are necessary for the rise of intelligence. Oxygen and moving land (plate tectonics) would conspire to make this place a poor location for life, at least complex multicellular life.