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Authors: Michael Specter

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That’s the approach Amyris has taken in its efforts to develop new fuels. “Artemisinin is a hydrocarbon and we built a microbial platform to produce it,” Keasling said. “We can remove a few of the genes to take out artemisinin and put in a different hydrocarbon to make biofuels.” Amyris, led by John Melo, who spent years as a senior executive at British Petroleum, has already engineered three molecules that can convert sugar to fuel. “It is thrilling to address problems that only a decade ago seemed insoluble,” Keasling said. “We still have lots to learn and lots of problems to solve. I am well aware that makes people anxious, and I understand why. Anything so powerful and new is troubling. But I don’t think the answer to the future is to race into the past.”

FOR THE FIRST four billion years, life on earth was shaped entirely by nature. Propelled by the forces of selection and chance, the most efficient genes survived and evolution ensured they would thrive. The long, beautiful Darwinian process of creeping forward by trial and error, struggle and survival, persisted for millennia. Then, about ten thousand years ago, our ancestors began to gather in villages, grow crops, and domesticate animals. That led to new technologies—stone axes and looms, which in turn led to better crops and the kind of varied food supply that could support a larger civilization. Breeding goats and pigs gave way to the fabrication of metal and machines. Throughout it all, new species, built on the power of their collected traits, emerged, while others were cast aside.

As the world became larger and more complex, the focus of our discoveries kept shrinking—from the size of the planet, to a species, and then to individual civilizations. By the beginning of the twenty-first century we had essentially become a society fixated on cells. Our ability to modify the smallest components of life through molecular biology has endowed humans with a power that even those who exercise it most proficiently cannot claim to fully comprehend. Man’s mastery over nature has been predicted for centuries—Bacon insisted on it, Blake feared it profoundly. Little more than one hundred years have passed, however, since Gregor Mendel demonstrated that the defining characteristics of a pea plant—its shape, size, and the color of the seeds, for example—are transmitted from one generation to the next in ways that can be predicted, repeated, and codified.

Since then, the central project of biology has been to break that code and learn to read it—to understand how DNA creates and perpetuates life. As an idea, synthetic biology has been around for many years. It took most of the past century to acquire the knowledge, develop the computing power, and figure out how to apply it all to DNA. But the potential impact has long been evident. The physiologist Jacques Loeb was perhaps the first to predict that we would eventually control our own evolution by creating and manipulating new forms of life. He considered artificial synthesis of life the “goal of biology,” and encouraged his students to meet that goal. In 1912, Loeb, one of the founders of modern biochemistry, wrote that “nothing indicates . . . that the artificial production of living matter is beyond the possibilities of science. . . . We must succeed in producing living matter artificially or we must find the reasons why this is impossible.”

The Nobel Prize-winning geneticist Hermann J. Muller attempted to do that. By demonstrating that exposure to X-rays can cause mutations in the genes and chromosomes of living cells, he was the first to prove that heredity could be affected by something other than natural selection. He wasn’t entirely certain that humanity would use the information responsibly, though. “If we did attain to any such knowledge or powers there is no doubt in my mind that we would eventually use them,” Muller wrote in 1916. “Man is a megalomaniac among animals—if he sees mountains he will try to imitate them by building pyramids, and if he sees some grand process like evolution, and thinks it would be at all possible for him to be in on that game, he would irreverently have to have his whack at that too.”

We have been having that “whack” ever since. Without Darwin’s most important—and contentious—contribution, none of it would have been possible, because the theory of evolution explained that every species on earth is related in some way to every other species; more important, we carry a record of that history in each of our bodies. In 1953, James Watson and Francis Crick began to make it possible to understand why, by explaining how DNA arranges itself. The language of just four chemical letters—adenine, guanine, cytosine, and thymine—comes in the form of enormous chains of nucleotides. When joined together, the arrangement of their sequences determine how each human differs from each other and from all other living beings.

By the 1970s, recombinant DNA technology permitted scientists to cut long, unwieldy molecules of nucleotides into digestible sentences of genetic letters and paste them into other cells. Researchers could suddenly combine the genes of two creatures that would never have been able to mate in nature. In 1975, concerned about the risks of this new technology, scientists from around the world convened a conference in Asilomar, California. They focused primarily on laboratory and environmental safety, and concluded that the field required only minimal regulation. (There was no real discussion of deliberate abuse—at the time it didn’t seem necessary.)

In retrospect at least, Asilomar came to be seen as an intellectual Woodstock, an epochal event in the history of molecular biology. Looking back nearly thirty years later, one of the conference’s organizers, the Nobel laureate Paul Berg, wrote that “this unique conference marked the beginning of an exceptional era for science and for the public discussion of science policy. Its success permitted the then contentious technology of recombinant DNA to emerge and flourish. Now the use of the recombinant DNA technology dominates research in biology. It has altered both the way questions are formulated and the way solutions are sought.”

Scientists at the meeting understood what was at stake. “We can outdo evolution,” said David Baltimore, genuinely awed by this new power to explore the vocabulary of life. Another researcher joked about joining duck DNA with orange DNA. “In early 1975, however, the new techniques hardly aspired to either duck or orange DNA,” Michael Rogers wrote in the 1977 book
Biohazard
, his riveting account of the meeting at Asilomar and of the scientists’ attempts to confront the ethical as well as biological impact of their new technology. “They worked essentially only with bacteria and viruses—organisms so small that most human beings only noticed them when they make us ill.”

That was precisely the problem. Promising as these techniques were, they also made it possible for scientists to transfer viruses—and cancer cells—from one organism to another. That could create diseases anticipated by no one and for which there would be no natural protection, treatment, or cure. The initial fear “was not that someone might do so on purpose,” Rogers wrote—that would come much later—“but rather that novel microorganisms would be created and released altogether accidentally, in the innocent course of legitimate research.”

Decoding sequences of DNA was tedious work. It could take a scientist a year to complete a stretch ten or twelve base pairs long (our DNA consists of three billion such pairs). By the late 1980s automated sequencing had simplified the procedure, and today machines are capable of processing that information, and more, in seconds. Another new tool—polymerase chain reaction—was required to complete the merger of the digital and biological worlds. Using PCR, a scientist can take a single DNA molecule and copy it many times, making it easier to read and manipulate. That permits scientists to treat living cells like complex packages of digital information that happen to be arranged in the most elegant possible way.

Mixing sequences of DNA, even making transgenic organisms, no longer requires unique skills. The science is straightforward. What came next was not. Using the tools of genomics, evolutionary biology, and virology, researchers began to bring dead viruses back to life. In France, the biologist Thierry Heidmann took a virus that had been extinct for hundreds of thousands of years, figured out how the broken parts were originally aligned, and then pieced them back together. After resurrecting the virus, which he named Phoenix, he and his team placed it in human cells and found that their creation could insert itself into the DNA of those cells. They also mixed the virus with cells taken from hamsters and cats. It quickly infected them all, offering the first evidence that the broken parts of an ancient virus could once again be made infectious.

As if experiments like those were not sufficient to conjure images of Frankenstein’s monster or
Jurassic Park
, researchers have now resurrected the DNA of the Tasmanian tiger, the world’s largest carnivorous marsupial, which has been extinct for more than seventy years. In 2008, scientists from the University of Melbourne in Australia and the University of Texas M. D. Anderson Cancer Center in Houston extracted DNA from two strands of tiger hair that had been preserved in museums. They inserted a fragment of a tiger’s DNA that controlled the production of collagen into a mouse embryo. That switched on just the right gene, and the embryo began to churn out collagen—marking the first time that material from an extinct creature (other than a virus) has functioned inside a living cell.

It will not be the last. A team from Pennsylvania State University, working with fossilized hair samples from a 65,000-year-old woolly mammoth, has already figured out how to modify that DNA and place it inside an elephant’s egg. The mammoth could then be brought to term in an elephant mother. “There is little doubt that it would be fun to see a living, breathing woolly mammoth—a shaggy, elephantine creature with long curved tusks who reminds us more of a very large, cuddly stuffed animal than of a T. rex,” the
New York Times
wrote in an editorial after the discovery was announced. “We’re just not sure that it would be all that much fun for the mammoth.” The next likely candidates for resurrection are our ancient relatives, the Neanderthals, who were probably driven to extinction by the spread of modern humans into Europe some forty thousand years ago.

All of that has been a prelude—technical tricks from a youthful discipline. The real challenge is to create a synthetic organism made solely from chemical parts and blueprints of DNA. In the early 1990s, working at his nonprofit organization the Institute for Genomic Research, Craig Venter and his colleague Clyde Hutchison began to wonder whether they could pare life to its most basic components and then try to use those genes to create a synthetic organism they could program. They began modifying the genome of a tiny bacterium called
Mycoplasma genitalium
, which contained 482 genes (humans have about 23,000) and 580,000 letters of genetic code, arranged on one circular chromosome—the smallest genome of any known natural organism. Venter and his colleagues then systematically removed genes, one by one, to find the smallest set that could sustain life.

He called the experiment the Minimal Genome Project. By the beginning of 2008, Venter’s team had pieced together thousands of chemically synthesized fragments of DNA and assembled a new version of the organism. Then, using nothing but chemicals, they produced the entire genome of
M. genitalium
from scratch. “Nothing in our methodology restricts its use to chemically synthesized DNA,” Venter noted in the report of his work, which was published in
Science
magazine. “It should be possible to assemble any combination of synthetic and natural DNA segments in any desired order.” That may turn out to be one of the most memorable asides in the history of science. Next, he intends to transplant the artificial chromosome into the walls of another cell, and then “boot it up,” to use his words—a new form of life that would then be able to replicate its own DNA, the first truly artificial organism. Venter has already named the creation Synthia. He hopes that Synthia, and similar products, will serve essentially as vessels that can be modified to carry different packages of genes. One package might produce a specific drug, for example, and another could have genes programmed to digest excess carbon in the atmosphere.

In 2007, the theoretical physicist and intellectual adventurer Freeman Dyson took his grandchildren to the Philadelphia Flower Show and then the Reptile Super Show in San Diego. “Every orchid or rose or lizard or snake is the work of a dedicated and skilled breeder,” he wrote in an essay for the
New York Review of Books.
“There are thousands of people, amateurs and professionals, who devote their lives to this business.” This, of course, we have been doing in one way or another for millennia. “Now imagine what will happen when the tools of genetic engineering become accessible to these people.”

He didn’t say if, he said when: because it is only a matter of time until domesticated biotechnology presents us with what Dyson describes as an “explosion of diversity of new living creatures. . . . Designing genomes will be a personal thing, a new art form as creative as painting or sculpture. Few of the new creations will be masterpieces, but a great many will bring joy to their creators and variety to our fauna and flora.”

Biotech games, played by children “down to kindergarten age but played with real eggs and seeds,” could produce entirely new species, as a lark. “These games will be messy and possibly dangerous,” he wrote. “Rules and regulations will be needed to make sure that our kids do not endanger themselves and others. The dangers of biotechnology are real and serious.”

I have never met anyone engaged in synthetic biology who would disagree. Venter in particular has always stressed the field’s ethical and physical risks. His current company, Synthetic Genomics, commissioned a lengthy review of the ethical implications of the research more than a year before the team even entered the lab. How long will it be before proteins engineer their own evolution? “That’s hard to say,” Venter told me, “but in twenty years this will be second nature for kids. It will be like Game Boy or Internet chat. A five-year-old will be able to do it.”

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