Creation (13 page)

It's here that life's first great schism occurs. Two sets of molecules grow to line the inside of separate rocky chambers that hold this brimming biochemistry. One will lead to bacteria; the second, to every other living thing. The biochemistry that has developed in these cells is shared, but from now on, as they evolve new powers, they build different types of membranes to house themselves, and new ways of maintaining the energetic difference between outside and in. There, stuck to the side of a gassy rock at the bottom of the ancient sea, cellular life begins.

This is a model. It is Bill Martin's plausible description of how genesis could have occurred based on what we know about simple life and the chemistry and geology of the vents. It's impossible to put a timescale on this transition. Roughly, we have a window of several hundred million years, somewhere between the earth-pummeled Late Heavy Bombardment and the fossil cells we can actually see, around 3.6 billion years old. Modern alkali vents are fairly stable, but rare. They may have abounded on the seafloors of the capricious young earth. Chemical reactions tend not to dawdle. Allowing a million years for two things to react gives ample opportunity for them not to—to be washed away. But this timescale provides the opportunity for the experiment to take place billions of times, over and over again in billions of pores, with infinite variables being tested over and over again. It is a conspiracy of chance made possible by the sheer numbers on offer. It only needs to have worked once, the jackpot in the chemical lottery.

We can't repeat the timescale, nor can we experiment in vents themselves. But we can model them. This is why Nick Lane's humble bioreactor is such an important experiment. It is an experiment in the purest sense, too, as he really doesn't know what will come out of it. The pores are seeded with iron sulfide (aka fool's gold), a catalyst that is present in the vents, which may speed up the energy transduction that is the beginning of metabolism. Just like in the vents, protons bubble up from the base and circulate through the labyrinthine pores. Each of many different biological processes is being tested individually, and the products examined. Lane is looking for the hallmarks of biological molecules—the bases of RNA and their component parts, amino acids that make up proteins, and the molecules that come from energy-harnessing metabolism. It is designed to find hints of biology built without enzymes, and at the time of this writing, this simulation is just beginning. The key to this experiment is that it is all far from equilibrium, just like life is, and just like the vents are. It won't make cells, but it might spontaneously generate signatures of the chemistry that underlies all living processes.

Although the definition might be elusive, we certainly know what life is when we see it. Life is physics, chemistry, and biology. That makes the attempts to recreate its origins a renaissance science. That also makes it contentious, because different experts will approach from the angle that makes the most sense to them. The quest to build life anew is to understand all of the things that life does, and to re-create them individually at first, then gradually align them and fuse them. Many of the pieces are being forged, all with different but vital characteristics: energy, information, reproduction, metabolism, evolution.

The journey from simple chemistry to more complex chemistry to biochemistry, from simple information to profoundly inscrutably sophisticated genetics, and from simple soapy bubbles to dynamic custom houses of membranes might seem unlikely. The astronomer and author Fred Hoyle once described the unlikelihood of the animation of chemistry as follows: “The chance that higher life forms might have emerged in this way is comparable to the chance that a tornado sweeping through a junkyard might assemble a Boeing 747 from the materials therein.” He goes on, in typically bombastic terms, to say that it is “nonsense of a high order.” In his book
Evolution from Space
, he made a calculation about the probability of the proteins of a most basic living cell arising spontaneously, and came up with the number one with forty thousand zeroes after it.
⁸
Hoyle believed in panspermia and used this calculation to dispute the origin of life's being the earthbound transition from chemistry to biology. It was a fallacious argument and has been refuted sensibly many times. Hoyle's errors include the assumption that modern proteins were the first in life. He assumes that the trial of building a working cell was sequential, not simultaneous. He might have been contemplating the twenty amino acids that emerged from the sludge of Stanley Miller's famous brew, all present and correct, ready to fall into line into a working, living entity.

But in the works of Gerald Joyce, Jack Szostak, John Sutherland, Nick Lane, Mike Russell, Bill Martin, and others, we now see emergent properties that are not improbable at all, and are a lot less mysterious than we once thought. The conditions of the infant earth, tested in modern labs, render self-creation unavoidable.

We see RNA whose origin is random sequence fulfilling the roles of early enzymes and early genes. We see cell-like bags summoned into being by nothing other than atomic forces. And we experiment to see the hallmarks of metabolism emerge from the effervescence of inanimate chemistry. As we march toward an increasingly sturdy model of genesis, the mysteries of creation once filled by deities inevitably give way to science. In the lab, at least, we see a foreshadowing of the process that has driven the spread of life for four billion years. Ribozymes undergo a form of Darwinian selection, as does the transition from simple membranes to complex. This is not to say that Darwin had miraculous prescient knowledge of chemistry a hundred years on from his death. It's merely that the process of natural selection that he first described is more powerful than he could have possibly imagined. And “whilst this planet has gone cycling on according to the fixed law of gravity,” as he wrote, a transition happened, driven by the power of a process that would one day lead directly to you. As we continue to explore the world of the cell, we are on the brink of seeing the start of this grand journey of life on Earth, the only living planet we know of. And such humble beginnings, too. Every muscle twitch, every breath, every thought, emotion, and sensation you've ever had, right down to the wince of pain from an insignificant paper cut, started its journey in a microscopic chamber at the bottom of the sea, four million millennia ago.

The Future of Life

Life, Not as We Know It

“What I cannot create, I do not understand.”

Richard Feynman, 1988

W
hat is the best way to find out how a thing works? There are a number of approaches, including observing how it behaves, or testing it (possibly to destruction or at least till it fails). But there is only so much you can learn from these techniques. To understand a thing of complexity you have to take it apart. A car mechanic cannot understand the complexities of the internal combustion engine merely by thrashing it on a racetrack. To understand an engine you must take it apart and see how the parts fit together, what each one does separately, and how they relate to one another.

Since before the discovery of the most basic unit of life in the late seventeenth century, the cell,
¹
biologists have spent plenty of their time observing and testing how living things work. But a much more instructive endeavor has been to take them apart. Leonardo da Vinci was an accomplished anatomist who drew many beautifully intricate diagrams of the insides of animals and people in order to determine structures and functions within our bodies. In the early seventeenth century William Harvey deduced the mechanisms of blood circulation by dissecting the fine construction of veins, arteries, and the animal and human heart.

Fifty years later, Antonie van Leeuwenhoek had discovered cells, the things from which all life-forms are built. As microscopes improved, the guts of these tiny bags of living matter were systematically unveiled and, in time, removed from the protective membranes that encase their innards. In the nineteenth century mere observation was supplanted by chemical detective work, and the composition of the components of cells—proteins and other essential ingredients of life—began to be described.

It was during the nineteenth century, with these chemical techniques, that DNA was first isolated, though it was almost a hundred years before its importance and its iconic double-helix structure were discovered. In 1869, a young doctor named Friedrich Miescher was working in Tübingen, Germany. As a result of the ongoing Franco-Prussian War, he had ready access to the pus-soaked bandages of wounded soldiers slowly rotting in a local hospital. Pus contains a surfeit of white blood cells called leucocytes, their purpose being to fight the determined invasion of disease-causing interlopers at an open wound. In extracting various ingredients from the fetid bandages, he isolated a chemical that contained significant quantities of the small molecular group phosphate. This particular cluster of five atoms is not normally detected in proteins, whose chemical composition had been well studied by this time. Therefore, Miescher figured his extract was different. He called it nuclein, as it came primarily from the nucleus of the soldiers' leucocytes, a separate compartment in the center of the cells of all complex life. Protein names tend to end in the letters -
in,
such as hemoglobin and insulin, so it is tempting to speculate that Miescher was still thinking of it in similar terms. His work was never really followed up, and it wasn't until many years later, when nuclein was shown to belong to an entirely different class of molecule, that it was identified as DNA.

In the twentieth century, biology matured into the study of ever-smaller components of cells. DNA was characterized famously by Watson and Crick using the data of Rosalind Franklin and Maurice Wilkins in 1953, and Crick, along with dozens of others, spent the next few years decrypting how vital information was stored inside the double helix. The workings of our complete set of DNA, the genome, were the focus of the grandest endeavor in biology: the Human Genome Project. That venture finished in the first decade of the twenty-first century with a complete read-through of the three billion letters of DNA in an average human, though the mysteries of human genomics continue to be explored.

Since Crick and Watson's landmark, the second half of the twentieth century was the era of molecular biology, and by the end of it the majority of all scientific research on Earth broadly concerned the molecules of life—DNA, its equally important cousin RNA, and proteins. Understanding the molecules and the language of life and their universal nature has profoundly transformed all aspects of our understanding of living organisms. As we explored in part one, DNA and molecular biology were the final bricks that cemented our understanding of the nature of evolution and provided a unifying mechanism by which we can trace our way back into the deep past, and to a single origin of life, a stem from which all life has grown.

It has also spawned a new way to examine living things. As we will discover in the following chapters, our solid understanding of the molecules of life has led to an era in which we can alter, manipulate, and effectively remix the basic genetic code of any living thing. We collect these related fields under the umbrella term
genetic engineering,
which has already begun to transform aspects of our lives. It has revolutionized the discovery of how diseases transpire, as we can alter the DNA of animals and cells to mimic those diseases and use those remixed cells as a test ground for bold new medical treatments.

If the biological twentieth century was concerned with taking cells apart to understand how they work, this newfound understanding has also given us the ability to put them back together again, but intelligently designed by us with specific purposes. Cells are minute manufactories, evolved over billions of years to have highly specialized functions—to construct bone, store memories, convert light into electricity in our eyes, or swallow invaders that cause us harm. They either are collected into a community performing in harmony to form an organism or, as is the case with most cells on Earth (bacteria and their lesser-known cousins archaea), live free as single entities.

The quotation at the beginning of this introduction, “What I cannot create, I do not understand,” is attributed to the great bongo-playing physicist and all-around master of science and science communication Richard Feynman. It was his last message to his students, written on his blackboard at Caltech at the time of his death in 1988. It is in the reassembly of the language of life that we are at a place beyond mere comprehension of living systems, one where life-forms are engineered tools. Genetic tinkering became wholesale engineering and now has evolved into a new field whose purpose is solely to create life-forms that serve as tools for humankind. It is known by the contranym synthetic biology.

Definitions in science are often imprecise and frequently unhelpful. Synthetic biology means different things to different people, and aspects of those definitions are discussed in the following pages. Scientifically, it is a direct descendant of genetic engineering, and often the overlap between the two is unclear. For that reason, I have looked at both in the course of exploring our newfound ability to create life-forms using parts of genes and cells taken from the toolbox that evolution has provided. And finally, as a postscript, I will explore the creation of entirely new molecules that fit into DNA but are not part of evolution's lexicon of new languages and new uses for the genetic code.

All of the creations of genetic engineering and synthetic biology are new to the inventory of life. Most of them feature minor modifications or small additions that add a new function to (or, indeed, knock an existing function out of) an organism. Almost all occur in bacteria, whose genetics are understood well enough that they have become essential equipment of the modern era of biology. Even so, synthetic biology is a new field, and many people may be unfamiliar with it.

In May 2010, the news was briefly—and unprecedentedly—besieged by a single synthetic cell. It was given a name, and photos of Synthia, as it became known, adorned front pages and television channels all over the world. After fifteen years of toil and roughly $40 million, the geneticist J. Craig Venter published a paper that described a bacterial cell his team had created. Its genome had been assembled not inside a parent cell, as with every other cell in history, but in a computer. The press swooned. One magazine put Venter as the fourteenth-most influential person on Earth, sandwiched between David Cameron, the current British prime minister, and the American politician Sarah Palin. Although it was a major landmark, Synthia was not quite part of the synthetic biology revolution that is beginning.

Craig Venter himself was keen to mark this event in grand terms. To illustrate our command over DNA and to distinguish Synthia (aka
Mycoplasma mycoides JCVI-syn1.0
) from naturally occurring bacteria, Venter and his team hid what video game players call an Easter egg in its genome, in the form of secret encrypted messages in the DNA of his creation. One of these was “What I cannot build, I cannot understand,” which fractionally misquotes Feynman. An unnamed member of Craig Venter's team had obtained it from the Internet, a source that on occasion has been known to be wrong. Errors aside, this Easter egg quotation served the purpose of stamping an indelible “watermark” into this bacteria, proving that it was unnatural in origin. It also showed that DNA can act as a data storage device, a means of encoding information that is not biologically relevant. We shall come to this emerging field in the afterword. Overall, this whole story was an impressive demonstration of just how far we have come in our technological ability to manipulate and build DNA.
²

Synthia owes its existence to the Minimal Genome Project.
Mycoplasma genitalium
is a minor parasite that causes minor burning and itching in infected men and women when they urinate. That's not what is interesting about it, though. Venter's interest in this cell is because it has a mere 517 genes, and a genome of only 582,000 letters of genetic code—bases (compared with 4.6 million bases for the more common lab microbe
E. coli
, or 3 billion for humans). After sequencing the first complete genome in 1995, Venter and his colleagues' second quarry was
M. genitalium
. This choice was no act of laziness, but the critical first step in Venter's next big idea. The plan was (and is) to determine the smallest number of genes and the minimum amount of genetic code required to sustain a living cell. Life originated with only a handful of basic genes, and they were copied and mutated for all subsequent life to flourish. But those first cells must have started with an entry-level set. Starting with the smallest known genome (at the time) made a lot of sense. The long-term plan was to establish the minimal amount of DNA required for a cell to exist and reproduce, so that they could use that genome as a foundation on which they could build new functions. Those functions were typically grand: for example, to address the environmental damage that our use of fossil fuels has brought upon the planet by building microbes that might produce hydrogen for fuel. There are a couple of reasons for building a cell from scratch rather than modifying an existing one. For example, cells can be controlled more precisely in defined conditions such as labs, and they can have singular purpose built into their genetic program so that the normal functions of cells are curtailed. But the primary reason is control: in principle, we can potentially control a synthetic cell far better than natural cells that we don't fully understand.

Synthia represents a proof of principle, that it is possible to construct an entire genome synthetically, albeit a very small one. And it is possible to get it into a cell, so that the cell functions and, crucially, reproduces like any other bacteria. More broadly, this saga shows the ambition of scientists to turn biology into an applied science, into engineering. It indicates that the molecular manufacturing required in synthetic biology is not at all easy, which is not surprising, given how young this field is. The protagonists of the purest form of synthetic biology have engineering as their key guiding principle and, even more specifically, the commoditized version of electrical engineering. These aims are not merely to investigate and understand how living processes function, but to re-create, remix, and build living organisms that address global problems.

With the publication of Venter's creation, the media brandished a curious mixture of teeth gnashing and misplaced triumphalism. The
Daily Mail
, a UK newspaper not known for nuanced reporting on scientific advances, ran the story with a headline that bellowed: “Scientist accused of playing God after creating artificial life by making designer microbe from scratch—but could it wipe out humanity?” The very straightforward answer to that question is no, as is inevitably the case when newspaper science headlines end with a question mark. Here is why: Synthia's genome was designed with fail-safe devices built into it. In general, these work in two ways. First, you can include genes that ensure your modified bacteria is only able to grow in a very specific blend of food that only the lab knows how to produce. Second, the genome from which Synthia's was copied and modified is based on a minor goat pathogen, one that causes udder infections. Venter's team inserted a chunk of DNA that renders the cell incapable of causing infection. Therefore, while it might be able to just about survive outside the lab in which it was created, it would not be able to thrive in its preferred habitat unless someone with molecular biology expertise further modified its genetic limitations. Could it wipe out humanity? No, but if a skilled geneticist was persistent and mean-spirited enough, it might well bother a goat.

The brouhaha was not limited to tabloid newspapers. Eminent professors weren't shy in joining in the hubris. Julian Savulescu, professor of ethics at Oxford University, told the
Guardian:

Venter is creaking open the most profound door in humanity's history, potentially peeking into its destiny. He is not merely copying life artificially . . . or modifying it radically by genetic engineering. He is going toward the role of a god: creating artificial life that could never have existed naturally.