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BOOK: A Brief History of Creation
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Though various teams had tried to find such a self-replicating RNA molecule, Szostak envisioned taking the concept one step further by building a true RNA organism. Building on an idea he had come up with alongside Italian biochemist Pier Luigi Luisi in 2003, Szostak wanted to work on building an actual RNA-based
cell
, one in which the RNA was housed in a lipid membrane.

According to Szostak's model, the first living thing might have been a naked RNA molecule. But the first living cell—FLO—would have needed a membrane for early evolution. Szostak saw two good reasons for this requirement. The first was that molecules that stay together evolve together. It seems unlikely that a single strand of RNA could do
all
of the various functions needed to propagate a cell. A small family of molecules might have been required, held inside a small bubble that forced them to collaborate. These molecules would copy each other and influence each other's evolution in mutually beneficial ways.

The second, closely related reason was the problem of freeloaders. An RNA molecule that was generally good at copying other RNA molecules in its environment would be beset by parasitic RNA molecules, few of which might actually contribute to the welfare of the pack. Enclosing the copying ribozyme in a cell with only its collaborators—the freeloading viruslike RNA molecules locked safely outside—would make the encapsulated ensemble much more efficient.

In all modern cells, membranes are composed of molecules known as amphiphiles. These molecules are made up of fats, like animal tallow and coconut oil, which form the basis of almost every soap and shampoo. When placed in water, under the right conditions, they have a natural tendency to spontaneously form bubbles ranging in size from the microscopic to the very large, which could have formed the basis of simple cell membranes. There may be good reason to suspect that such lipid bubbles were abundant
on the primitive Earth, even before life had devised ways of making them. Meteorites like Murchison have been found to contain similar molecules, and small bubble-like structures form from the organic “goo” common in such meteorites. This goo could have spontaneously formed cell-like compartments in shallow pools on the Earth.

To realize this vision of FLO, Szostak developed a novel approach harnessing the power of natural selection. Using billions of small random RNA molecules encased in tiny lipid bubbles, he simply lets them compete in test tubes just as Spiegelman's monsters did. The ones that copy themselves well should grow at the expense of those that do not. Szostak hopes that, at some point, a set of these RNA molecules will spontaneously solve the problem of making each other and the membrane itself from simpler precursors that the scientists supply. The result will be a living, evolvable RNA-based organism: an RNA-world re-creation of FLO.

A
COUPLE OF BLOCKS
from Boston's Charles River, on the seventh floor of a research building owned by Harvard Medical School, a microscope sits in a room barely larger than a walk-in closet. On the door hangs an old photograph of Mahatma Gandhi. Dressed in traditional garb, the Hindu holy man and leader of India's struggle for independence is bent over and peering into a small microscope. Inside, the room is barren except for a single chair and a small table upon which sits an actual microscope. Above it, a picture cut out of a magazine is taped to the wall. It is a picture of a protocell as imagined by Szostak, brightly colored and simple, devoid of all the typical machinery of the cell except for a single strand of RNA. Next to it are four simple words: “A Cell Is Born.”

If Jack Szostak and his team are successful in their quest to create a living model of his vision of FLO, it is there, in that little room, that the first self-replicating RNA-based cell will be seen by a human being. It will be a species more primitive than any currently living on Earth, a monumental discovery. It will undoubtedly be greeted by a flood of sensational press coverage. In the eyes of many, the problem of the origin of life will have been largely solved.

Yet history shows that a great enigma will likely remain. It will be the same dilemma embodied by the question once posed by the physicist Enrico Fermi to his old friend Harold Urey: Is this how it
could
have happened, or how it
did
happen?

Carl Sagan was fond of recalling a story from a public panel discussion he had taken part in Chicago in 1960. A member of the audience had asked the panelists when scientists would solve the mystery of the origin of life by actually duplicating the process in a test tube. The first panelist said it would be in about a thousand years. The second said three hundred. Gradually, the numbers got smaller and smaller until one scientist said it had already been done.

The question of the origin of life has always provoked unrealistic expectations in those who look to science to explain the natural world. Similar to the early Christians who waited for a Rapture they were sure was just around the corner, so, too, have believers in science expected that the solution to one of its greatest mysteries was on the verge of being revealed. And so have they waited for hundreds of years.

Depending on one's perspective, the answer to the question of how life began has always been right around the corner—or so incredibly difficult that it may never be definitively answered. Science has no doubt made enormous strides toward understanding the transition from nonlife to life. The mystery has attracted some of the world's greatest minds; no doubt it will continue to do so. It could well be that definitive answers
are
just around the corner. There is likewise a good chance that the question will remain unsolved, at least in our lifetimes. We simply do not know whether the transition from nonlife to life took a week or a month or five hundred million years. A process like this may require such a vast amount of time that it will never be observable in a laboratory.

We do know that science will never stop searching for the answer. Perhaps that search has already yielded something important. Perhaps it has told us something about the nature of science and even of ourselves.

*
Venter and his team encoded a series of quotations in the synthetic genome as a puzzle. These included a quote from James Joyce's
Portrait of the Artist as a Young Man
, “To live, to err, to fall, to triumph, to recreate life out of life.” Two other quotes included were “See things not as they are, but as they might be,” from
American Prometheus
, the story of Robert Oppenheimer and the creation of the atomic bomb, and “What I cannot build, I cannot understand,” reportedly the last words left written on the physicist Richard Feynman's blackboard at the time of his death. They also encoded a link to a website where amateur cryptologists could report their having unraveled the puzzle. Venter and his team had a good practical reason to include the quotations: the coded messages were proof of the bacteria's synthetic origin.

†
There has been some progress in synthesizing such a molecule. In 2011, a British team led by Philip Holliger announced the synthesis of an RNA polymerase, made out of RNA—not protein—that could copy another RNA molecule ninety-five nucleotides long.

EPILOGUE

Men in their generations are like the leaves in the trees. The wind blows and one year's leaves are scattered on the ground; but the trees burst into bud and put on fresh ones when the spring comes round. In the same way one generation flourishes and another nears its end
.

—HOMER,
The Iliad
, c. 1250
BC

 

I
N HIS FAMOUS LECTURE
at the Sorbonne, Louis Pasteur made an observation about the nature of science and the role of the scientist. Science, he said, is an impartial arbiter. The true scientist must strip himself of all preconceived ideas. About the subject at hand, spontaneous generation, Pasteur said one could come to no other conclusion through science than to arrive at the necessity of a divine role in the creation of life.

Roughly a century and a half later, the evolutionary biologist Richard Dawkins stood in the laboratory of one of the world's most influential geneticists and delivered a speech that began in almost identical terms. Science, he said, does not take sides; it looks only for objective truth. But here Dawkins, an ardent atheist, diverged from Pasteur, a Catholic and vitalist. For Dawkins, one could draw no other conclusion than to say that the first emergence of life was purely the product of natural laws, completely devoid of the supernatural.

Dawkins was standing in the laboratory of Craig Venter, who had helped map the human genome and had led a team that actually reverse-engineered a living organism. Pasteur delivered his lecture at a time when there was as yet no notion of the existence of nucleic acids and the gene was no more than a concept. The world has changed dramatically since Pasteur's day. Synthetic biology has opened up the inner machinery of living organisms. The engines
that drive life can be seen, scrutinized, and manipulated. In our lifetimes, the cost and ease of making a synthetic living thing may become so trivial that it can be something amateur scientists do in their garages. We understand the world and the forces that govern it far better than human beings just a century ago could ever have imagined.

In many ways, our understanding of the origin of life has always been a function of the available tools and technology with which we could make sense of the world. The microscope opened up new worlds to the human beings of the seventeenth century. The printing press of the nineteenth century opened up those worlds to vastly more people. The explosion of technological innovation in the twentieth century—radiometric dating, gene sequencing, exploration of the solar system, to name just a few—has likewise transformed our understanding of biology, and of the origins of biology on this Earth.

But technological progress is not all that has changed since Pasteur's famous Sorbonne lecture. Speaking at Francis Crick's funeral in 2004, Michael Crick said that his father had wanted to be remembered for finally putting to rest the theory of vitalism, the idea that some uncrossable chasm existed between the living and nonliving. Noting that the word “vitalism” was not recognized by Microsoft Word, he said, “Score one for Francis.”

The balance of power between science and theology in society has shifted. Nothing symbolizes that shift more than a trip Sidney Fox made to the Vatican in 1964 to advise Pope Paul VI on evolution and the most modern scientific concepts of the origin of life. The pope's predecessor, Pius XII, had already announced that evolution was not incompatible with church teachings, marking a slow but steady return to the spirit of Saint Augustine, who some two millennia earlier had said that the church would not be served by appearing ignorant of the natural world. The march toward an acceptance of scientific explanations for the origin of life seems inevitable. In 1996, Pope John Paul II alluded to the “recognition of evolution as more than a hypothesis.” Less than two decades later, Pope Francis warned against thinking of God as “a magician, with a magic wand able to do everything.”

In a sense, the world has come full circle. With the notable exception of the United States, religion in most of the developed world has largely ceded to
science much of the responsibility for explaining how the physical world functions. Gone are the days when Redi and van Helmont had to tread carefully in the shadow of religious authority, or a man like Robert Chambers was forced to publish anonymously for fear of religious retribution. Even in America, where biblical literalists remain an influential minority, scientists are almost entirely free to follow the pursuit of knowledge wherever it may lead.

T
ODAY, TENS OF MILLIONS
of dollars are spent researching the problem of the origin of life at scores of eminent labs around the world. Every year, new results generate a great deal of excitement that scientists may finally be on the brink of solving the central mystery of biology. A never-ceasing drumbeat of stories appears in the press about every new idea. Often these are given outsized significance. Even the notion of panspermia is routinely resurrected as an exciting and somehow new idea. We want to believe that science has a firm grip on the central problem of biology. The reality, though, is that it is very difficult to say how close we are to understanding the answer to this most vexing of questions.

Yet the search for answers has already taught us an enormous amount about the world and the way it works. Since the Reinaissance, scientists involved in that search have transformed our understanding of biology. They have driven our first steps into the cosmos and spurred our exploration of the microscopic workings of molecular biology. Along the way, our vision of the universe and our place within it have been fundamentally reshaped.

The long saga to understand the origin of life may hold some subtler lessons as well. It may tell us something deeper about the nature of science, even something about our very nature as human beings. Most of the characters in the great saga to unravel the origin of life did not merely set out to answer a question. Many of them used science to prove or disprove a worldview.

Redi didn't drink snake venom just to make a point about the deadliness of snake venom. He was trying to show that reason was superior to superstition. The atheist supporters of John Needham did not look at his work and say, “This is good science.” They looked into his microbial broth and saw a pathway around the need for God. The religious looked at Needham's broth in much
the same way, and saw a threat to the existential meaning upon which they had centered their lives. Sidney Fox looked at his proteinoid microspheres and saw a vindication of his life's work, something he could never let go of, even when faced by a mountain of opposition. Nearly every scientist who attempts to explain purported microbial fossils—in ancient rocks or in meteorites—sees something different. These tiny structures often become the scientific equivalent of a Rorschach test.

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