First Contact (9 page)

Benner's Gainesville lair is hardly the highly organized, precision-driven lab you might expect. Certainly the area where his almost twenty-person team of chemists and biochemists do their molecular slicing and dicing is well controlled, and the work of experts in paleogenomics (who read the evolutionary history of life-forms through their genomes) requires mind-numbing precision. But the heart of the operation, where the sparks fly, is Benner's office. At its center is a fifty-two-inch Sharp Aquos computer screen connected to a smaller one—the blackboard on which he diagrams chemical systems. He goes at the task with the focus and energy of an artist captured by a moment of creativity, and the screen can soon fill up with hundreds of connected
C
's (carbon) and
H
's (hydrogen) and
P
's (phosphorus) as they interact and loop around to form known or possibly synthesized biochemical cycles. Benner, talking and writing nonstop, sits in an oversize pinkish reclining chair, taped in the back where the material is cracked. On prominent display around him is a sampling of his collection of minerals and fossils of fish and plants, ferns and small mammals. Benner has been a fan of both rocks and fossils since he was a boy, and each object has a story.

The boron-based rock on his shelf, for instance, captures one of his scientific eureka moments. Benner had been on Catalina Island, off Los Angeles, with a group of geologists, and he was leading them through some
experiments involving the sugar ribose, a mineral with calcium in it, and water. The goal was to find a way to keep the combination from turning into brown tar, which seldom has anything useful in it from a biological perspective. This is a significant issue in the origins-of-life world because ribose is the R of RNA, and it has to be stable enough at some point to bond with the other elements. (Stanley Miller, of the Scripps Research Institute, outside San Diego—the deceased godfather of origins of life experimentation—famously found some precursors to the building blocks of life in 1954, opening the door to what was assumed to be a fairly imminent test-tube creation of life from nonlife. But it never happened and in 1995 Miller basically said it couldn't—primarily because ribose is unstable in the water that is assumed necessary to support life.) Benner long knew that the element boron at least temporarily blocked the decomposition of ribose in water, but he had never before thought to throw it into the origin-of-life chemical mix. But he did in Catalina, and the ribose did not immediately start the usual quick slide into tar when a pinch of boron was added. Instead it stayed clear, and a very excited Benner believed he had found a way to allow the essential ribose to be created on early Earth while still keeping water in the picture. This epiphany didn't solve the question of how life formed from nonlife, but it offered a plausible explanation for how one of many obstacles may have been overcome. When I first heard Benner speak at an astrobiology conference, he made a quick but quite serious aside suggesting that boron really could be central to the creation of life—even though it is one of the less common elements on Earth and across the universe.

The origins-of-life world has two competing schools. One says that the Last Universal Common Ancestor (or LUCA) formed as “life” when genetic material came together and self-replication could begin. The other view is that metabolism—the process of taking in the energy of food, using it, and then expelling a waste product—was the essential first step. Benner is in the genetics camp, which is why the origins-of-life component of his lab spends its time searching for ways to form the scaffolding of RNA or DNA out of nonliving parts. So many confounding factors are involved
that biochemists like Benner are among the most skeptical about finding life beyond Earth. From the perspective of physicists, astronomers, biologists, and others in the astrobiology world, extraterrestrial life is a given. But to the chemists and biochemists working to actually get life started, the prospects are not as tangible. Making life from nonlife has turned out to be extraordinarily hard.

Benner says he assumes the actual origin of life—the pathway that created the first organisms that could feed, could replicate themselves, and then could evolve by producing mutant replications and keeping those that turned out to be useful—will remain unknowable. But finding another way that nonlife turned into life would be an entirely acceptable, actually enormous historical triumph, because it would provide the indispensable “proof of principle” that cutting-edge scientists are always looking for.

“Look, we know that life evolved from nonliving sources because otherwise we're left with divine intervention—which is hardly an acceptable explanation for most scientists. That's what keeps some of us going. It will be enormously difficult to find how it happened, but we know it
did
happen, either on Earth or elsewhere and then transplanted here.”

The field has seen progress, even if it hasn't had the big breakthrough that many are looking for. In 2009, the journal
Science
published the results of work in the Scripps lab of Gerald Joyce, who with Tracey Lincoln produced an RNA enzyme (a protein that increases the rate of chemical reactions) that was a super replicator capable of building copies of itself over and over again, something never done before with RNA. This high-powered enzyme, refined and concentrated through cultures, met the primary goal of being able to perpetually replicate itself, as well as to mutate and then pass on the genetic blueprint of that mutation to other RNA. “This is the only case outside biology where molecular information is being passed through the generations [and] has become immortal,” is how Joyce put it.

Joyce is now working to expand the functions of that immortal replicator and to see if it could survive and prosper in a more varied and complex system, if the stronger enzymes created by the lab could be challenged
to invent new functions, just as RNA material presumably had to do on the early Earth. If he succeeds, he said, the lab will have indeed created life. “We believe genetic material that can respond to increasingly complex challenges represents life.” I later asked Benner if that would meet his criteria, and he gave a quick “yes” as well.

But synthetic biology has an Achilles heel, hidden in plain sight: All of the researchers in the field make their creations using strands of preformed DNA and RNA that they can buy from a supply house. Manipulating those strands to make something out of them that can copy itself and somehow get energy from its environment would be an enormous achievement, but it would still require the scaffolding of genetic material to be delivered by overnight mail in a vial. Clearly, that's not how life started. Producing “life” in a lab may soon turn out to be possible, but it would require not only a lot of already formed complex molecules but also a lab full of scientists and equipment. Synthetic biology is science at its most imaginative and sophisticated, but at bottom it can't exist without the kind of intelligent designer that would give comfort to those who subscribe to a religious view of the origins of life—it requires a Creator. So the goal is a proof of concept, not a re-creation of the origins of life. Matt Carrigan, an origins-of-life researcher in Benner's lab, talks of research that would “jump the chasm,” that would put together unprocessed molecules—not from the supply store—in a way that would allow them to begin life. But that kind of biochemistry seems very far in the future.

•   •   •

Ironically, it is the search for life beyond Earth, rather than the quest to synthesize it in a lab, that may hold the greatest promise for determining what constitutes life. On Earth, we have one essential model of life: Every living thing takes in energy and expels waste, maintains a thermodynamic balance, and, most remarkably, uses the same twenty amino acids to form the proteins that do all the heavy lifting within cells. What's more, all life on Earth uses the nucleotides adenosine triphosphate (ATP) and adenosine
diphosphate (ADP) to store and distribute energy within cells. It's been extraordinarily difficult—somewhat like imagining a new color in the spectrum—to put together any respectable theories of what a significantly different extraterrestrial life might look like and how it might work. The National Academy report on “weird life” put it succinctly: “As Carl Sagan noted, it is not surprising that carbon-based organisms breathing oxygen and composed of 60 percent water would conclude that life must be based on carbon and water and metabolize free oxygen.”

So any discovery of a life-form not descended from LUCA would provide this remarkable bonus: Finding Extraterrestrial Life 2.0 would make far more clear what Earthly Life 1.0 actually entails, and what is needed for something to be alive. It's a head-spinning conclusion, counterintuitive in the extreme. But the discovery of extraterrestrial life, of life as we don't know it, may be the only way to finally define what actually constitutes life on Earth.

This is the story of an iconic but largely dismissed experiment that suddenly came back after fifty-five years to offer clues to a new generation of scientists about the spark that may have ignited life on Earth.

The most famous of all origin-of-life experiments was conducted in 1952 by University of Chicago graduate student Stanley Miller and his professor, Nobel Prize winner Harold Urey, in a small chemistry lab at their school. The experiment consisted of mixing together heated water with the gases believed at the time to have made up the atmosphere of the early Earth, and then exposing them to a prolonged electric shock. It was done inside a closed circuit of glass tubes and flasks hung on a metal scaffold, with no computers to drive and monitor the process, no gas chromatographs for high-tech analysis. But the results in its day were jaw-dropping: It showed that complex amino acids, essential organic building blocks of life, could be formed out of simple and common gases, water, and electricity. Prior to Miller-Urey, divine creation or the spontaneous generation of life were widely believed to be the only possible explanations for life on Earth. Darwin himself had dodged the issue in
On the Origin of Species
. Now science had demonstrated exactly how some of the key molecules needed for life could have come into being through natural processes, making plausible overnight the theory that life came together over eons in the early Earth's great primordial vat of oceanic soup.

The results were published at an especially heady time—just three weeks after James Watson and Francis Crick described the double helix
structure of our DNA. That landmark discovery ignited the field of genetics and quickly led to new insights by the score, including the fact that our biological inheritance is passed on through genes that code the twenty amino acids essential for life. These same twenty molecules in turn provide the design for the workhorse proteins that actually make things happen in a cell—quickly breaking down compounds for energy and building new useful ones, creating a scaffolding within the cell, an immune system, and an ability to reproduce. And it's not just we humans that need these particular twenty amino acids (out of a possible universe of five hundred or more). These twenty compounds are also found in every living creature ever studied. Amino acids are not themselves living, but they are an essential organic component of proteins and therefore life, and the Miller-Urey experiment proved they could be formed, through tried-and-true chemistry, from inorganic parts. It was the beginning, in concept at least, of what would later be called “abiogenesis,” “exobiology,” and finally “astrobiology.”

The experiment gave support to those looking for an entirely naturalistic and secular explanation for the origin of life on Earth, but it also did the same for those thinking about life beyond Earth. As Carl Sagan put it, the experiment was “the single most significant step in convincing many scientists that life is likely to be abundant in the cosmos.” If life could be painstakingly assembled from nonliving things on Earth via the known laws of physics and chemistry, then why wouldn't the same processes produce life elsewhere?

But Miller-Urey didn't fare as well, over time, as Watson-Crick. While Miller-Urey gave impetus and energy to the study of prebiotic chemistry and inspired many researchers to push further in the field, scientists gradually came to believe that the gases used to make the amino acids in the experiment were actually not present on early Earth (some 4 billion years ago) in the forms and concentrations the researchers used. What's more, the carbon dioxide and nitrogen now believed to have dominated the atmosphere of early Earth form nitrites, which destroy amino acids as quickly as they come together. Miller-Ureyites found that the nitrite problem was largely solved if large amounts of iron and calcium minerals were
also present, but there's no evidence that was the case. The findings were consequently challenged and in time pretty much ignored. The Watson and Crick work became the foundation of the burgeoning fields of molecular biology, genetics, and genetic engineering.

And so it was without much fanfare that in 2005, after Stanley Miller died, his onetime graduate student and later collaborator at Scripps, Jeffrey Bada, began closing down and packing up Miller's old lab. His interest was in preserving important correspondences to and from his mentor and colleague, and also to search for interesting amino acids Miller may have collected. Bada later recalled coming across an old cigar box on a shelf, noting that it had some old and seemingly used vials in it, and then storing it somewhere without much thought. Only several years later did Bada learn what he had overlooked, during a fortuitous meeting with another origins-of-life colleague, Antonio Lazcano of the University of Mexico. The two were preparing to give back-to-back talks at a conference in Texas, and they went up to their hotel room to compare slides and images on their computers. They wanted to make sure their talks wouldn't overlap. Bada saw something most unexpected on Lazcano's screen.