Creation (11 page)

If DNA is a twisted ladder, the two essential components are the rungs and the struts. In RNA, which is only a single strand, it is like a ladder cut vertically in half. In order to get the individual letters of code to link up into working molecules, they have to link up to the struts of the ladder. This third component is a linker made of phosphate—a combination of phosphorus and oxygen atoms. The struts, meanwhile, are made of types of sugar molecules: the
R
in RNA stands for the sugar ribose, and the
D
in DNA for deoxyribose, which is the same except for one less oxygen atom. Each molecule of these sugars is attached to one of the letters,
A, C, G,
or
T
(or
U
in RNA); and when these sugar molecules are stacked up, they form the backbone, the ladder's struts. In DNA two backbones pair up, in RNA they remain as a single strand. It is the shape of these molecules that determines their behavior. For example, uracil is a small, hexagonal ring of atoms, and it links up with its sugar, ribose, which is a pentagonal molecule. Together, they make up a single rung of RNA, and these will get linked together by phosphates with the other bases to make a piece of genetic code. This brief aside into possibly painful chemical structures helps us to realize why re-creating life anew is a tricky business. Only these precise shapes will act as part of living cells, but there are plenty of other ways these molecules could be rearranged. An atom in the wrong position, a molecular appendage in a different place and you don't get DNA or RNA; you don't have life.

The trouble is that biological chemistry in cells just happens, whereas we have to try quite hard to emulate it. While we can observe and deconstruct the mechanism that cells use to manufacture these molecules, for the purposes of studying the origin of life we need to understand their synthesis before those manufactories were present. Outside the foundries of our cells, getting the rings of sugar and uracil to link up has proven to be a pain.

Chemistry is an ancient science and has well-worn pathways of synthesis. Making complex molecules is frequently done by laying one stone at a time, building up to the final product. Some steps are harder than others, and atoms have to be cajoled into forming bonds where we want them to be rather than somewhere easier. Gentle coaxing can persuade two reluctant atoms to link up on the pathway. Yet in the case of making uracil for use in RNA, this stepwise chemical synthesis has proven unfruitful, as it has a reluctance to link its two component rings.

John Sutherland and his team are also at the LMB in Cambridge. His approach to this problem is a bold step, at least in terms of chemistry dogma. In a landmark study in 2009, Sutherland successfully bypassed the obstruction by taking an entirely different route.
¹¹
The traditional approach is to keep the production of the two components—the ribose rings and the uracil ring—separate, as both processes produce a tar of products. Mixing them together, it was assumed, would result in a chemical sludge containing many sugars and a lot of other stuff, but not much uracil. To get around this, Sutherland ignored the prejudice of that stepwise pathway to sludge and decided to mix the ingredients together initially. This technique is called systems chemistry, in which instead of assembling the parts of a complex molecule one after another, and purifying them after each step, all of the ingredients are mixed at the same time. It is in some ways reminiscent of Stanley Miller's experiments in the 1950s, which produced amino acids in abundance from a stock of ingredients supposedly present in the young earth. It's categorically different, though, in that it is not merely mixing together ingredients to see what will emerge. The production of uracil in this way is heavily designed to do exactly that, in an environment that conceivably was present. It's not often that scientists use a word such as
plausible
in the title of a paper, but in Sutherland's case it fits their model: “Synthesis of Activated Pyrimidine Ribonucleotides in Prebiotically Plausible Conditions.” I have been dismissive of the idea of primordial soup in the previous chapter, on the grounds that it is not energetically plausible for a self-sustaining living system to emerge from a chemical swill. This is different, as it is a mechanism for building up the elements of living things, in this case the language of genetics.

Sutherland's approach works—uracil is formed—and is summed up with his comment, “Complexity is in the eye of the beholder.” His reasoning is that it must have happened in the past without the assistance of a chemistry lab or the cellular machinations of biology. This new pathway is itself of great importance, but somewhat reserved for chemistry wonks. It turns out that the key missing seasoning was phosphate, which had the effect of jamming sugar production, but nurturing the linking of the two rings to form uracil.

Yet the approach says something significant about attitude in science. Sutherland's thinking is rather radical. For the first time, instead of thinking about the chemical conditions of the early earth and trying to emulate them to make uracil, he and his team figured out a way to synthesize uracil and then postulated that these conditions were likely to have been the chemical swill from which code built itself. After all, we already know the outcome on the early earth: it happened, regardless of how hard we find repeating it. Uracil and all the elements of genetic code were created somehow and somewhere, and if we can recreate that, we potentially know more than we did about what the early earth was actually like.
¹²

Our prejudices about the difficulty in nonbiological creation of complex molecules was also challenged in 2008 when a team led by Zita Martins at Imperial College London isolated uracil in the Murchison meteorite. That 220-pound rock had fallen to the Australian earth in 1969 and has been subject to scrutiny ever since, not least because it's big, which means there's lots of material to work on. It's also full of carbon, and so of interest to astrobiologists, many of whom suggest that extraterrestrial rocks might have delivered some if not many of the chemical components to Earth. Certainly, other bases and amino acids have been found in meteorites; given the flow of these boulders from space during the Late Heavy Bombardment, this might be a plausible supply. Either way, the presence of extraterrestrial uracil shows again that its synthesis is perfectly possible no matter how hard we find it to do.

It's difficult to shake people's prejudices, but there is no place for dogma in science. When explaining his new pathway, Sutherland faced vocal criticism from entrenched chemists decrying the simultaneous formation of the ingredients, insisting on the traditional view that synthesis should be incremental and stepwise, not derived from a chemical brew. He now jokes that this criticism is the “Dem Dry Bones” model, in which each element is created ready to be assembled into a whole: “The foot bone connected to the leg bone.” So how does evolution produce a lower limb? By connecting a preformed foot and leg, of course: “Now, hear the word of the Lord!”

With these experiments the emergence of the universal language of life is not solved, but they reveal a pathway that looks rather plausible. The language of life is a staggering example of natural design. Not only does it have the ability to encode the wonders of the living world, it is built with a natural buffer in it—one that encourages evolution, but not too radically. We now have a grasp of how this code came to be. We have credible roots from basic chemicals to the letters of the language, we have simple RNA molecules that act like genes and promote their own replication, and we have a reason to think that DNA would be a better data storage device and so would ultimately replace the RNA world, where the genetic code could have plausibly originated. The conundrum at the origin of the central dogma—DNA makes RNA makes protein—is partially undone by the heroic ability of RNA to do the jobs of the others in that equation: code and function. With ribozymes, the mechanics of gene duplication is handled by RNA itself; it doesn't need the proteins that perform this vital function (as well as others). But the broader chicken-and-egg problem remains. Replication in cells from Luca onward requires energy. Therefore, underlying the RNA world, the transition to DNA, and the establishment of cells and life as we know it, must have been a source of energy that could be captured and manipulated to form the basis of all the energy-vampire processes that cells need. And here, we find ourselves in hot, deep water.

Genesis

“If you come to think of it, what a queer thing Life is! So unlike anything else, don't you know, if you see what I mean.”

P. G. Wodehouse,
“Rallying Round Old George”

I
t's a heavy load, but you wear it so casually. You read these words with the accumulated weight of humankind's achievements behind you. For all the wonder of the genetic and cellular circuits that allow you to function, accumulated over billions of iterations in the unbroken lineage of cells, we're also a species that is the product of our culture. We invent, compose, trade, share, learn, and create. But more important, we carry these things with us through families, through groups, and across our species. Cultural evolution is not restricted to the descent of genes through pedigrees. We can learn from anyone else and acquire their skills without a genetic bond. There's a lucrative intellectual trade in declaring that one of the things humans do is what defines us as a species. It wasn't the invention of tools that switched us from simpler ancestors to modern humans, though that was part of the process. Earlier human species constructed simple tools, such as flint chippers or crude ax heads. Plenty of animals use tools, too, from otters' using stones to crack mussels to crows' wielding sticks to dig out a fat grub from a log. What's important is not that we do uniquely human things, but that we continue to do them. Humans, above all,
accumulate
culture.

You are the sum of your parts and our species, genes passed from parent to child for generations, and culture and ideas passed from human to human in all sorts of directions. This should be obvious, just as there wasn't one moment that made you who you are. We love to pretend that there are lightbulb moments in which something flipped and a character or an event was forged—Rosa Parks choosing to remain seated on a bus; an unnamed Chinese student defying a tank. They are iconic moments but don't describe the flow of history. Life—your life, any life—is not merely a series of incidents. It is the accumulation of everything you experience.

The beginning of life was just that, too. The transition from chemistry to biology was the accumulation of the things that life does—feeding, copying, reproducing, and so on. At some point in the earth's history there were just chemicals, and at a later point there was life. The most exciting question in science is how that transition happened.
¹

There are many components to the rebuilding of life from the bottom up, and the quest for a simple answer to a problem of immense complexity will probably be futile. How it happened the first time and how it will happen the second, and subsequent, times will be different. But the challenge of origin-of-life initiatives is to emulate creation in plausible and credible scenarios. That means thinking not just about what the processes were that transformed chemistry into biology, but also where.

From Foreign Shores

Why should we have such a conservative system of biology: one code, one mechanism, one central dogma? We now know that RNA probably acted as a precursor to the more robust system in place today. Francis Crick speculated that the universality of DNA was a frozen accident, a system that worked and was locked into place, forever it seems, to the exclusion of any alternatives. Once in place, any changes would either be lethal to the bearers of a novel vital system or outcompeted rapidly by existing life. Why did the code become fixed? The truth is that we don't really know. Studies have worked up ideas that it was no accident, and that the four-letter code and the twenty-amino-acid lexicon are optimally balanced at a point where positive and deleterious mutation permits evolution to occur successfully. There is a seemingly simpler explanation, one that Crick was briefly seduced by. It is this: the code didn't evolve at all. It was delivered here, already functional but frozen, from somewhere else. In this case, “somewhere else” means outer space.

This is one of the vaguely more scientific versions of an origin-of-life idea called panspermia, which maintains that the earth was seeded with living things at some point in the deep past, and evolution of species ensued. Cast aside the images of space aliens, belligerent gray bipeds with spindly bodies and bulbous heads. The aliens described by panspermia's advocates would be simple, bacterial-type cells, or even simpler, the mechanics of cellular life to be harnessed by whatever the Archaean planet had available. Carried on comets or meteors, they would act as the seeds of evolution, an infection from the stars. Upon successful delivery, they were free to engage in evolution by natural selection.

Francis Crick, writing with Leslie Orgel, authored a paper entitled “Directed Panspermia” in 1973, not just outlining the possibility of extraterrestrial delivery of the seeds of life but also arguing that they were sent here deliberately by intelligent beings. Crick and Orgel were drawn to the idea of directed panspermia largely because of the inadequacies of existing ideas about the origin of the genetic code. It's a strangely tongue-in-cheek study, contemplating aloud the limitations of space flight and speculating with wise foresight on the discoveries of planets beyond our solar system. At that time none was known; at the time of this writing we are up to almost a thousand.
²

It's not difficult to see the appeal of panspermia, though scientifically, it is neither plausible nor credible. Even today, in this era of local galactic calm, around thirty thousand tons of debris descends onto our planet each year, mostly in the form of dust disintegrated in the atmosphere. Showers can be seen burning up in the sky at the right time of year, such as the Perseids in each northern hemisphere summer. We even know of interplanetary relocation, at least in tiny quantities.
³

Once in a blue moon, a big one hits, like in Murchison, Australia, in 1969. Mercifully rarely, a colossal one lands, like in Chicxulub sixty-five million years ago. These rocks are from outer space, formed when larger space rocks collide and send their debris on a crash trajectory with Earth. These events are now uncommon, especially in the case of the carbon-rich meteor that landed in Murchison, loaded with molecules that we know are essential for life on Earth. But leading up to our best estimates of Luca's Earth was the intense and relentless meteorite activity of the Late Heavy Bombardment. Millions of tons of space rocks were deposited here over a period of millions of years, to the extent that a small proportion of the earth's mantle is made up of interstellar rocks. It would potentially only take the survival of one single cell to seed all that followed.

Alas, the attractiveness of an idea is of no consequence in science. It's the data that counts, and therefore it's easy to deal with panspermia as an explanation for the origin of life on Earth. There is simply no evidence for it. While it is appealing in a sci-fi sense, we have no evidence for life ever having survived beyond the orbit of the moon, and there it was only us as tourists.

That is not to say life does not exist beyond this pale-blue dot we call home,
⁴
but we have never seen it. Not in the claims of alien abductees, nor in the microscopic bobbles of rocks from Mars,
⁵
nor in the credible scientific hunt by SETI, the Search for Extraterrestrial Intelligence. The rate at which we discover Earth-like planets is rocketing as we get better at looking for them. But for the time being, we are alone.

Certainly, we see many of the ingredients of life in space. We are, it is important to remember, in space, formed in space, and in formation, part of the solar system. To ignore this is to deny the fact that our existence is determined by the space in which the earth exists. Often, the press reports a new discovery concerning the extraterrestrial origin of one of Earth's constituent parts. Invariably, these studies are reported, with excitable glee, to be extraordinary. The true revelation of these discoveries is that they were previously unknown, not that delivery via comets or meteors might be inherently surprising. We now know that many of the ingredients of life, the component parts, are present in space, including amino acids and even, as discussed in the previous chapter, elements of genetic code. These are important scientific discoveries, especially for the study of the origin of life. They show that the chemistry which produces biological molecules occurs outside biology. That means that synthesis of those components is not limited to Earth. And it describes a mechanism of delivery, whereby comets or meteorites can bear these chemical parts and potentially deliver them to our surface.

Earth has continually and unsurprisingly (though inconsistently) been the recipient of things that fill our local space. If we make a clear delineation between “Earth” and “not Earth,” then the ingredients that make up our living planet are going to be manufactured in one of these two places. Is it therefore a surprise that water, methane, and other chemicals that figure as elemental standards in biochemistry originated off-world?

Panspermia is seductive because it looks like a simpler explanation, one that does not need the patchy, incomplete time line we currently have in place. But in fact it's not simpler; it's simply a dodge. If there were evidence for the transfer of life from elsewhere in the universe to Earth, and there were no other plausible explanations, then panspermia might have some legs. But it doesn't address the question of how life started on Earth, and simultaneously provides no evidential support for its starting anywhere else. Parsimony enforces the notion that it might look like a simpler explanation than our very incomplete alternatives. But it is far from being the case, because it requires not only that life abounds or at least exists in the universe, but that it is also based on DNA. We simply have no evidence to support that. As it is, there are other, better avenues worth exploring; they have their own problems, but at least they are scientific routes, ones that can be tested and retested. Reliance on extraterrestrial life as the delivery boy for a cosmic egg is neither necessary nor sufficient for the origin of life. For now, and for the foreseeable future, life from beyond our pale-blue dot must remain in the dominion of science fiction.

Containment

All cellular processes, including the mode of information replication, are underwritten by a system that harnesses and uses energy, and we will come to that shortly. But first, there is another issue to deal with. Cells are discrete units of life, either in an organism or free-living, and so their information and metabolism have to be kept separate from the rest of the universe. We therefore have the problem of the origin of the membrane. Containment of the guts of a cell is an absolute part of being alive, and it is easy to think that the cell membrane is merely a container, a sheer balloon in which the machinations of life are contained. Certainly, containment of a cell's vital organs is essential, as it has the effect of concentrating chemical reactions that maintain life. But cells exist as part of an environment, not apart from it. The cell membrane is more akin to a custom house, an interface that monitors and controls the import and export of all the goods and messages a cell needs. This immense complexity allows an individual cell to exist in its environment or with the other cells in its host creature. This exchange comes in the form of a highly complex network through which traffic constantly flows, even when resting, and is carefully regulated through gated pores, pumps, and channels that stud the surface of a cell like seeds on a strawberry.

Cell membranes are built from fatty molecules called phospholipids. These look like split pins used for holding sheaves of hole-punched paper together: they have a water-attracting head and two legs that repel water. At Harvard, Jack Szostak's work is centered on how the cellular membrane came to be. He experiments with simpler molecules with only one tail, to see how they behave, and how they might help us understand the formation of the first cells through self-organizing behavior.

When Szostak mixes together a delicate blend of these fatty molecules, they do something that is simultaneously remarkable and not. They self-organize into a tiny bubble, about the same size as a bacterial cell, a hundredth of a millimeter wide. It's remarkable to us, because they look a bit like cells spontaneously forming out of straightforward chemicals. It's unremarkable, for the reason that they do this is because they can.
⁶

The fatty acids have a bulbous head and zigzaggy tail, and this combination makes them schizophrenic in their behavior. The atoms in the head are arranged so that they like butting up against water. The tails are quite the opposite, and repel water. But the tails also attract one another. In the right solution, a watery one, they therefore jostle together into two regimented lines, tails facing inward, and heads in the water. At the right concentration, this line will expand in all directions and link up to form a sphere. The nature of those fatty acids is such that they are chemically content when organized into this kind of membrane. As soon as that happens, there is an inside and everything else.

Modern cell membranes are studded with pumps, channels, aerials, and receivers to ensure a healthy contact with the extracellular world. Biological mailboxes lie embedded in the membrane to receive input signals from around the body and local environment, and strong anchors link up neighboring cells to hold tissue together. All of these membrane tools maintain living order within the cell and within the organism. Szostak's simple membranes are a long way from this highly evolved interface. But the first cells would not have access to that complex machinery. Part of the challenge of engineering spontaneous self-organization is to start with simple molecules and evolve more complex behaviors upward. Szostak calls his creations protocells, and many of the things they do are similar to what cells do. If you feed them, they grow and divide. They spontaneously absorb simple genetic molecules, short fragments of things similar to DNA. When they do, this absorption triggers growth and fission. If you heat them up and cool them down, they not only survive intact but DNA inside also undergoes a type of replication, which can stimulate growth and division of the whole.