The Best American Science and Nature Writing 2010

by Tim Folger

  Keasling, too, believes that the nation needs to consider the potential impact of this technology, but he is baffled by opposition to what should soon become the world's most reliable source of cheap artemisinin. "Just for a moment, imagine that we replaced artemisinin with a cancer drug," he said. "And let's have the entire Western world rely on some farmers in China and Africa who may or may not plant their crop. And let's have a lot of American children die because of that. Look at the world and tell me we shouldn't be doing this. It's not people in Africa who see malaria who say, whoa, let's put the brakes on."

  Artemisinin is the first step in what Keasling hopes will become a much larger program. "We ought to be able to make any compound produced by a plant inside a microbe," he said. "We ought to have all these metabolic pathways. You need this drug: OK, we pull this piece, this part, and this one off the shelf. You put them into a microbe, and two weeks later out comes your product."

  That's what Amyris has done 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 gene, to make biofuels." Amyris, led by John Melo, who spent years as a senior executive at British Petroleum, has already engineered three microbes that can convert sugar to fuel. "We still have lots to learn and lots of problems to solve," Keasling said. "I am well aware that makes some 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 4 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 insured that they would thrive. The long, beautiful Darwinian process of creeping forward by trial and error, struggle and survival, persisted for millennia. Then, about 10,000 years ago, our ancestors began to gather in villages, grow crops, and domesticate animals. That led to stone axes and looms, which in turn led to better crops and a varied food supply that could feed a larger civilization. Breeding of 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.

  By the beginning of the twenty-first century, our ability to modify the smallest components of life through molecular biology had endowed humans with a power that even those who exercise it most proficiently cannot claim to fully comprehend. Human mastery over nature has been predicted for centuries—Francis Bacon insisted on it, William Blake feared it profoundly. Little more than a hundred years have passed, however, since Gregor Mendel demonstrated that the defining characteristics of a pea plant—its shape, its 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. The physiologist Jacques Loeb considered artificial synthesis of life the goal of biology. In 1912 Loeb, one of the founders of modern biochemistry, wrote that there was no evidence that "the arti ficial production of living matter is beyond the possibilities of science" and declared, "We must either succeed in producing living matter artificially, or we must find the reasons why this is impossible."

  In 1946, 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 sure that people would use that 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 said. "Man is a megalomaniac among animals—if he sees mountains he will try to imitate them by pyramids, and if he sees some grand process like evolu tion, 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."

  The theory of evolution explained that every species on Earth is related in some way to every other species; more important, we each carry a record of that history in our body. 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, cytosine, guanine, and thymine—comes in the form of enormous chains of nucleotides. When they are joined, the arrangement of their sequences determines how each human differs from all others 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. As promising as these techniques were, they also made it possible for scientists to transfer viruses—and microbes that cause cancer—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. In 1975 scientists from around the world gathered at the Asilomar Conference Center, in northern California, to discuss the challenges presented by this new technology. They focused primarily on laboratory and environmental safety and concluded that the field required little regulation. (There was no real discussion of deliberate abuse—at the time, there didn't seem to be any need.)

  Looking back nearly thirty years later, one of the conference's organizers, the Nobel laureate Paul Berg, wrote, "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."

  Decoding sequences of DNA was tedious. It could take a scientist a year to complete a stretch that was ten or twelve base pairs long. (Our DNA consists of 3 billion such pairs.) By the late 1980s, automated sequencing had simplified the procedure, and today machines can process that information in seconds. Another new tool —polymerase chain reaction—completed 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 to 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.

  Using such techniques, 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 and the University of Texas M. D. Anderson Cancer Center, in Houston, extracted DNA from tissue that had been preserved in the Museum Victoria, in Melbourne. They took a fragment of DNA that controlled the production of a collagen gene from the tiger and inserted it into a mouse embryo. The DNA switched on just the right gene, and the embryo began to churn out collagen. That marked the first time that any material from an extinct creature other than a virus has functioned inside a living organism.

  It will not be the last. A team from Pennsylvania State University, working with hair samples from two woolly mammoths—one of them 60,000 years old and the other 18,000—has tentatively 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 Times editorialized soon after the discovery was announced. "We're just not sure that it would be all that much fun for the mammoth."

  The ultimate goal, however, is to create a synthetic organism made solely from chemical part
s and blueprints of DNA. In the mid-1990s, Craig Venter, working at the Institute for Genomic Research, and his colleagues Clyde Hutchison and Hamilton Smith began to wonder whether they could pare life to its most basic components and then use those genes to create such an organism. 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 cell that has been grown in laboratory cultures. Venter and his colleagues then re moved genes one by one to find a minimal set that could sustain life.

  Venter called the experiment the Minimal Genome Project. By the beginning of 2008, his 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 from scratch the entire genome of Mycoplasma genitalium. "Nothing in our methodology restricts its use to chemically synthesized DNA," Venter noted in the report of his work, which was published in Science. "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 understated asides in the history of science. Next Venter intends to transplant the artificial chromosome into the walls of another cell and then "boot it up," thereby making a new form of life that would then be able to replicate its own DNA—the first truly artificial organism. (Activists have already named the creation Synthia.) Venter 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 carbon in the atmosphere.

  In 2007 the theoretical physicist Freeman Dyson, after having visited both the Philadelphia Flower Show and the Reptile Show in San Diego, wrote an essay in the New York Review of Books noting that "every orchid or rose or lizard or snake is the work of a dedicated and skilled breeder. 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."

  It is only a matter of time before domesticated biotechnology presents us with what Dyson described 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," Dyson 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."

  Life on Earth proceeds in an arc—one that began with the big bang and evolved to the point where a smart teenager is capable of inserting a gene from a cold-water fish into a strawberry to help protect it from the frost. You don't have to be a Luddite—or Prince Charles, who, famously, has foreseen a world reduced to gray goo by avaricious and out-of-control technology—to recognize that synthetic biology, if it truly succeeds, will make it possible to supplant the world created by Darwinian evolution with one created by us.

  "Many a technology has at some time or another been deemed an affront to God, but perhaps none invites the accusation as directly as synthetic biology," the editors of Nature—who nonetheless support the technology—wrote in 2007. "For the first time, God has competition."

  "What if we could liberate ourselves from the tyranny of evolution by being able to design our own offspring?" Drew Endy asked the first time we met in his office at MIT, where, until the summer of 2008, he was assistant professor of biological engineering. (That September he moved to Stanford.) Endy is among the most compelling evangelists of synthetic biology. He is also perhaps its most disturbing, because, although he displays a childlike eagerness to start engineering new creatures, he insists on discussing both the prospects and the dangers of his emerging discipline in nearly any forum he can find. "I am talking about building the stuff that runs most of the living world," he said. "If this is not a national strategic priority, what possibly could be?"

  Endy, who was trained as a civil engineer, spent his youth fabricating worlds out of Lincoln Logs and Legos. Now he would like to build living organisms. Perhaps it was the three well-worn congas sitting in the corner of Endy's office, or the choppy haircut that looked like something he might have got in a tree house, or the bicycle dangling from his wall, but when he speaks about putting together new forms of life, it's hard not to think of that boy and his Legos.

  Endy made his first mark on the world of biology by nearly failing the course in high school. "I got a D," he said. "And I was lucky to get it." While pursuing an engineering degree at Lehigh University, Endy took a course in molecular genetics. He spent his years in graduate school modeling bacterial viruses, but they are complex, and Endy craved simplicity. That's when he began to think about putting cellular components together.

  Never forgetting the secret of Legos—they work because you can take any single part and attach it to any other—in 2005 Endy and colleagues on both coasts started the BioBricks Foundation, a nonprofit organization formed to register and develop standard parts for assembling DNA. Endy is not the only scientist, or even the only synthetic biologist, to translate a youth spent with blocks into a useful scientific vocabulary. "The notion of pieces fitting together—whether those pieces are integrated circuits, microfluidic components, or molecules—guides much of what I do in the laboratory," the physicist and synthetic biologist Rob Carlson writes in his new book, Biology Is Technology: The Promise, Peril, and Business of Engineering Life. "Some of my best work has come together in my mind's eye accompanied by what I swear was an audible click."

  The BioBricks registry is a physical repository, but it is also an online catalogue. If you want to construct an organism or engineer it in new ways, you can go to the site as you would to one that sells lumber or industrial pipes. The constituent parts of DNA—promoters, ribosome-binding sites, plasmid backbones, and thousands of other components—are catalogued, explained, and discussed. It is a kind of theoretical Wikipedia of future life forms, with the added benefit of actually providing the parts necessary to build them.

  I asked Endy why he thought so many people seem to be repelled by the idea of constructing new forms of life. "Because it's scary as hell," he said. "It's the coolest platform science has ever produced, but the questions it raises are the hardest to answer." If you can sequence something properly and you possess the information for describing that organism—whether it's a virus, a dinosaur, or a human being—you will eventually be able to construct an artificial version of it. That gives us an alternate path for propagating living organisms.

  The natural path is direct descent from a parent—from one generation to the next. But that process is filled with errors. (In Darwin's world, of course, a certain number of those mutations are necessary.) Endy said, "If you could complement evolution with a secondary path, decode a genome, take it offline to the level of information"—in other words, break it down to its specific sequences of DNA the way one would break down the code in a software program—"we can then design whatever we want, and recompile it," which could permit scientists to prevent many genetic diseases. "At that point, you can make disposable biological systems that don't have to produce offspring, and you can make much simpler organisms."

  Endy stopped long enough for me to digest the fact that he was talking about building our own children. "If you look at human beings as we are today, one would have to ask how much of our own design is constrained by the fact that we have to be able to reproduce," he said. In fact, those constraints are significant. In theory, at least, designing our own o
ffspring could make those constraints disappear. Before speaking about that, however, it would be necessary to ask two essential questions: What sorts of risk does that bring into play, and what sorts of opportunity?

  The deeply unpleasant risks associated with synthetic biology are not hard to imagine: who would control this technology, who would pay for it, and how much would it cost? Would we all have access or, as in the 1997 film Gattaca, which envisaged a world where the most successful children were eugenically selected, would there be genetic haves and have-nots and a new type of discrimination—genoism—to accompany it? Moreover, how safe can it be to manipulate and create life? How likely are accidents that would unleash organisms onto a world that is not prepared for them? And will it be an easy technology for people bent on destruction to acquire? "We are talking about things that have never been done before," Endy said. "If the society that powered this technology collapses in some way, we would go extinct pretty quickly. You wouldn't have a chance to revert back to the farm or to the pre-farm. We would just be gone."