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How Did It All Begin?
The Self-Assembly of Organic Molecules and the Origin of Cellular Life (1 of 4)

Introduction
Movies are the myths of late-20th century western culture. Because of the power of films like ET to capture our imagination, we are more likely than past generations to accept the possibility that life exists elsewhere in our galaxy. Such a myth can be used to sketch the main themes of this chapter, which concern the origin of life on the Earth.

Imagine that 4 billion years ago, intelligent beings evolved on an Earth-like planet in the solar system of a neighboring star. After ten million years of evolution, they have solved the problems of interstellar travel and aging. Virtually immortal family groups set out to explore the galaxy and almost immediately discover a solar system associated with a nearby star only 80 light years away from their home planet. They find that the third planet is rich in the primary elements of life — carbon, hydrogen, oxygen and nitrogen — which are present in the atmosphere in the form of carbon dioxide (CO₂), molecular nitrogen (N₂) and water vapor (H₂O). They decide to spend a few centuries studying this planet, which they consider to be a possible model of their own primordial world as it was four billion years in their past.

They learn that the planet gained most of its mass through a process called accretion, in which gravitational attraction causes dust particles to gather first into small asteroid-sized planetesimals, which then undergo immensely energetic collisions to form ever larger planetary bodies. A single moon looms in the sky, the result of one such collision during the final stages of accretion. The planet and its moon were molten after the collision, reaching temperatures of volcanic lava which degraded all organic compounds, leaving only their elements in the form of volatile gases. Additional carbon dioxide and water vapor continued to pour into the atmosphere through volcanoes that allowed outgassing from the planet's interior. The planetary and lunar crusts soon cooled by radiating heat into outer space, so that the moon's hardened surface began to preserve the accumulating record of impacts over the several hundred million years that followed the moon-forming collision event.

Now the global temperature has fallen to the point that water has condensed into vast, shallow oceans that virtually cover the planetary surface, with lava and pumice islands rising from undersea volcanic regions. Because of the very high atmospheric pressure of carbon dioxide, the temperature of the oceans is still well above the boiling point of water on their home planet. The planet is devoid of life, sterilized by the heat energy released by the original collision and later giant impacts. But the impacts have largely ceased, and the temperature continues to drop to the point at which organic carbon compounds remain stable for days, years, then decades. Some of these compounds are continuously synthesized at the planet's surface by a variety of chemical reactions, often using light as an energy source, while others are delivered by the infall of microscopic dust particles that is still adding the last few kilometers to the planet's diameter. As a result, organic substances begin to accumulate in the shallow seas, then become more concentrated by evaporation of tide pools and adsorption to mineral surfaces in submarine geothermal regions. The visitors take samples of the foamy material in the tide pools and examine it with their powerful microscopes. There is nothing alive, but they are surprised to find that some of the organic compounds have spontaneously aggregated into a variety of structures, including long molecules called polymers and microscopic bubbles. What could this mean?

The visitors fly away at faster than light velocities to visit other stars and solar systems, but return several hundred million years later to see what is happening on the third planet. (Because they can travel at supraluminal velocity, only a few years have passed in ship time.) This time they are astonished to discover that something remarkable has occurred. Instead of a sterile environment, the seas now teem with microbial life that has already begun to change the planet's surface and atmosphere. Comets and meteorites still bombard the planet, but now tens of millions of years separate the giant impacts and their energies hardly disturb the robust microbial life that has invaded every available niche.

Could their own versions of bacteria have somehow infected the planet during their last visit? A bit worried, the visitors again take samples and determine that the new life has an entirely different genetic code than their own, so it is not something they accidentally released. Apparently the spontaneous self-assembly processes they observed earlier produced enormous numbers of microscopic structures, a few of which increasingly were able to use the energy and nutrients available in the environment to reproduce their structures. But because several hundred million years have passed, the visitors missed the exact point in time at which this occurred! Frustrated, they depart for further exploration, hoping to find other primitive planets where they might have a chance to observe the origin of life. Another 3.5 billion years pass, and they return once again to see what has transpired. By this time they have discovered that planets with liquid water and life are common in the galaxy, so they are not surprised to find that primitive yet intelligent organisms now inhabit a place called California. When their space ship is observed they must quickly depart, accidentally leaving behind one of their younger family members...

Evidence related to the origin of life
Just kidding about that last part. But even the mythical visitors were astonished, as we should be, that the life process can begin spontaneously on an utterly sterile planet, as long as the environment has liquid water, organic carbon compounds, and energy. How does life begin? This is one of the remaining great questions facing science, a question so daunting that it has tended to inhibit serious scientific inquiry. Even Darwin once noted that "It is as absurd to think about the origin of life as it is to think about the origin of matter." But now, 150 years after Darwin expressed his concern, we do have a pretty good idea about the origin of matter. And we understand living cells in remarkable detail, even to the point that we have begun to manipulate the genetic blueprint of life and will soon know the entire sequence of 3 billion nucleotide bases in the human genome. But we still don't know how the life process began on the early Earth.

On the other hand, we can make some informed guesses, something not possible fifty years ago when the first research on life's origins began. The main point to be made here is that certain kinds of molecules have physical and chemical properties that allow them to self-assemble into orderly structures, and these are the molecules used by living cells. The self-assembly process seems to defy our intuitive expectation from the laws of physics that everything on average becomes more disordered (i.e., entropy increases). For instance, it is easy to calculate that it would be impossible for a specific protein ever to be produced by chance in the lifetime of the universe, and therefore conclude that a supreme being designed all proteins. However, one can make the same argument with a soap bubble. A bubble can't exist, according to the laws of chance, yet they are a common occurrence.

A number of recent scientific advances have provided a more coherent picture of the events leading up to the origin of life. This integrated vision has given rise to a new field called astrobiology, defined as the investigation of life in the universe, and takes into account our new understanding that life on the Earth is part of a universal process. The following question-answer format indicates the things we know with a fair degree of confidence, that now provide a framework for developing and testing hypotheses related to the origin of life.

Where does matter come from?
All atoms heavier that hydrogen and helium, including the elements important in living systems (carbon, oxygen, nitrogen, phosphorus and sulfur) are produced are produced in stars by nuclear fusion reactions. The atoms are then blown out into interstellar space toward the end of a star's lifetime when the star explodes as a nova or, more rarely, a supernova. The atoms then form molecules and dust particles and gather into the enormous clouds that have been visualized by the Hubble Telescope in extraordinary detail. The dust particles, composed largely of silicate minerals, are called interstellar grains. The grains are coated thin layers of ice and frozen gases like carbon dioxide, carbon monoxide, ammonia and methanol, as well as a variety of more complex organic compounds. The last point is among the most significant new discoveries about the interstellar medium. That is, organic compounds composed of carbon and the other biogenic elements are not limited to the Earth and its neighboring planets in our solar system, but are present wherever stardust gathers into interstellar clouds. We live in an organic universe.

Where do stars and solar systems form?
These clouds are the birthplaces of new generations of stars. During star formation, gravity causes portions of the clouds to form rotating disks with the star at the center. Kilometer-sized objects called planetesimals are produced by gravity-driven accretion of dust within the disk, and the planetesimals undergo increasingly violent collisions to produce larger planets. Our own moon is the result of such a collision between the primitive Earth and another planet the size of Mars or larger. We now have convincing evidence of a dozen Jupiter-sized planets around other stars, and the search is on for Earth-like planets.

What are sources of organic matter on planets?
During late accretion of Earth-like planets, organic compounds and water are delivered to planetary surfaces by comets and meteors. Surprisingly, a fraction of the organic compounds are able to stay intact during their arrival in the Earth's atmosphere. We can still see the delivery of organic compounds to the Earth's surface in the form of carbonaceous meteorites, both large and microscopic. It is likely that other organic compounds were synthesized in the Earth's atmosphere, because experiments have been conducted that reproduce the process under simulated prebiotic conditions. However, because the Earth's atmosphere now contains highly reactive oxygen as a result of photosynthetic activity, if organic compounds were synthesized by abiotic processes today they would be rapidly degraded by oxidation.

What is meant by self-assembly?
Certain organic compounds have the capacity to react with each other to form more complex molecules such as hydrocarbons, amino acids and simple sugars. Some of these can spontaneously self-assemble into membrane structures, and others can polymerize into molecules similar to proteins and nucleic acids. These in turn form larger self-assembled structures such as the double helix of DNA. Because there were no genes or enzymes available on the prebiotic Earth to direct the metabolism and reproduction characteristic of living organisms, the first forms of life must have been produced through a spontaneous self-assembly process.

How did catalytic activity become incorporated into the earliest forms of life?
Most life on the Earth today depends on protein catalysts called enzymes, which like all catalysts can greatly increase the rates at which reactions proceed. Catalysts are essential to life, but what were the first catalysts? They were probably not proteins, because protein synthesis requires DNA and other chemicals combined in a process much too complex to occurred spontaneously. However, we now know that certain kinds of ribonucleic acid (RNA) also have catalytic activity, behaving like protein enzymes. These are called ribozymes, and they considerably simplify our thinking about the beginning of life. We no longer need to consider that entire cells complete with DNA, RNA, ribosomes and protein synthesis somehow appeared. Instead, we can conceive of a primitive RNA system that could grow, reproduce and evolve, showing all the properties we associate with the living state.

When did life begin?
Evidence in the form of microscopic fossils has convincingly shown that bacterial life was abundant in shallow seas about 3.5 billion years ago. Other evidence from measurements of stable isotopes of carbon suggest that even simpler forms of life existed 3.8 billion years ago. If so, it follows that life can begin in as little time as 100 million years, since the Earth's surface was probably still too hot for any conceivable form of life over 4.0 billion years ago.

Where did life begin?
The origin of life must have occurred in an environment where the temperature was low enough to permit liquid water to exist. Some examples include tide pools or sub-surface sites similar to a hydrothermal vent or a geothermal hot spring. Liquid water is required for life as we know it, since only water can provide a universal medium in which self-assembly processes and metabolism can occur. The temperature of the site was likely to have been higher than prevails on the Earth today. We now know that microbial populations can inhabit environments once thought impossible, where temperatures range up to the boiling point of water. This greatly expands the possible range of sites for the origin of life, and suggests that living microorganisms could be present in deep hydrothermal regions under the Martian crust, or even on Europa, which is now believed to have ice-covered oceans of liquid water.