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.”
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 “grey 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 a world 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. “Only a deity predisposed to cut-and-paste would suffer any serious challenge from genetic engineering as it has been practiced in the past. But the efforts to design living organisms from scratch—either with a wholly artificial genome made by DNA synthesis technology or, more ambitiously, by using non-natural, bespoke molecular machinery—really might seem to justify the suggestion” that “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. It was a startling question—and it was meant to startle. Endy is synthetic biology’s most compelling evangelist. He is also perhaps its most disturbing, because, while he displays a childlike eagerness to start building new creatures, he insists on discussing both the prospects and dangers of this new science 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 structural engineer, is almost always talking about designing or building something. He spent his youth fabricating worlds out of Lincoln Logs and Legos. What he would like to build
now are living organisms. We were sitting in his office at the Massachusetts Institute of Technology, where until the spring of 2008, he was assistant professor in the recently formed department of biological engineering. (That summer, he moved to Stanford.) Perhaps it was the three well-worn congas sitting in the corner of Endy’s office, the choppy haircut that looked like something he might have gotten in a treehouse, or the bicycle dangling from his wall, but when he speaks about putting new forms of life together, it’s hard not to think of that boy and his Legos.
I asked Endy to describe the implications of the field and why he thought so many people are repelled by the idea of creating new organisms. “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. For instance, now that we can sequence DNA, what does that mean?” Endy argues that 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—you will eventually be able to construct an artificial version of it.
“That gives us an alternate path for propagating living organisms,” he said. “The natural path is direct descent from a parent—from one generation to the next. But that is an error process—there are mistakes in the code, many mutations,” although in Darwin’s world a certain number of those mutations are necessary. “If you could complement evolution with a secondary path—let’s decode a genome, take it offline to the level of information”; in other words, let’s break it down to its specific sequences of DNA the way we would the code in a software program—“we can then design whatever we want, and recompile it. 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, not to mention alternate versions of ourselves. Humans are almost unimaginably complex, but if we can bring a woolly mammoth back to life or create and “boot up” a synthetic creature made from hundreds of genes, it no longer seems impossible, or even improbable, that scientists will eventually develop the skills to do the same thing with our species. “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,” Endy said. “In fact, those constraints are quite significant. But by being able to design our own offspring we can free ourselves from them. Before we talk about that, however, we have to ask two critical questions: what sorts of risks does that bring into play, and what sorts of opportunities?”
The deeply unpleasant risks associated with synthetic biology are not hard to contemplate: who would control this technology, who would pay for it, and how much would it cost? Would we all have access or, as in Gattaca, would there be genetic haves and have-nots? 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? After all, if Dyson is right and kids will one day design cute backyard dinosaurs, it wouldn’t take much imagination for more malevolent designers to create organisms with radically different characteristics. “These are things that have never been done before,” said Endy. “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 prefarm. We would just be gone.”
Those fears have existed since we began to transplant genes in crops. They are the principal reason why opponents of genetically engineered food invoke the precautionary principle, which argues that potential risks must always be given more weight than possible benefits. That is certainly the approach suggested by people like Thomas of ETC, who describes Endy as “the alpha Synthusi ast.” But he added that Endy was also a reflective scientist who doesn’t discount the possible risks of his field. “To his credit, I think he’s the one who’s most engaged with these issues,” Thomas said. Endy hopes that’s true, but doesn’t want to relive the battles over genetically engineered food, where the debate has so often focused on theoretical harm rather than tangible benefits. “If you build a bridge and it falls down you are not going to be permitted to design bridges ever again,” he said. “But that doesn’t mean we should never build a new bridge. There, we have accepted the fact that risks are inevitable. When it comes to engineering biology, though, scientists have never developed that kind of contract with society. We obviously need to do that.”
Endy speaks with passion about the biological future; but he also knows what he doesn’t know. And what nobody else knows either. “It is important to unpack some of the hype and expectation around what you can do with biotechnology as a manufacturing platform,” he said. “We have not scratched the surface—but how far will we be able to go? That question needs to be discussed openly. Because you can’t address issues of risk and society unless you have an answer. If we do not frame the discussion properly we will soon face a situation where people say: Look at these scientists doing all these interesting things that have only a limited impact on our civilization, because the physics don’t scale. If that is the case, we will have a hard time convincing anybody we ought to be investing our time and money this way.”
The inventor and materials scientist Saul Griffith has estimated that between fifteen and eighteen terawatts of energy are required to power our planet. How much of that could we manufacture with the tools of synthetic biology? “The estimates run between five and ninety terawatts,” Endy said. “And you can figure out the significance of that right away. If it turns out to be the lower figure we are screwed. Because why would we take these risks if we cannot create much energy? But if it’s the top figure then we are talking about producing five times the energy we need on this planet and doing it in an environmentally benign way. The benefits in relation to the risks of using this new technology would be unquestioned. But I don’t know what the number will be and I don’t think anybody can know at this point. At a minimum then, we ought to acknowledge that we are in the process of figuring that out and the answers won’t be easy to provide.
“It’s very hard for me to have a conversation about these issues,” he continued. “Because people adopt incredibly defensive postures. The scientists on one side and civil society organizations on the other. And to be fair to those groups, science has often proceeded by skipping the dialogue. But some environmental groups will say, ‘Let’s not permit any of this work to get out of a laboratory until we are sure it is all safe.’ And as a practical matter that is not the way science works. We can’t come back decades later with an answer. We need to develop solutions by doing them. The potential is great enough, I believe, to convince people it’s worth the risk.
“We also have to think about what our society needs and what this science might do,” he continued. “We have seen an example with artemisinin and malaria. That’s only a first step—maybe we could avoid diseases completely. That could require us to go through a transition in medicine akin to what happened in environmental science and engineering after the end of World War II. We had industrial problems and people said, ‘Hey, the river’s on fire—let’s put it out.’ And after the nth time of doing that people started to say, ‘Maybe we shouldn’t make factories that put shit into the river. So let’s collect all the waste.’ That turns out to be really expensive because then we have to dispose of it. Finally, people said, ‘Let’s redesign the factories so that they don’t make that crap.’ ” (In fact, the fire that erupted just outside Cleveland, Ohio, on the Cuyahoga River in June 1969 became a permanent symbol of environmental disaster. It also helped begin a national discussion that ended in the passage of the Clean Water Act, the Safe Drinking Water Act, and many other measures.)
“Let’s say I was a whimsical futurist,” said Endy—although there is nothing whimsical about his approach to science or to the futu
re. “We are spending trillions of dollars on health care. Preventing disease is obviously more desirable than treating it. My guess is that our ultimate solution to the crisis of health care costs will be to redesign ourselves so that we don’t have so many problems to deal with. But note,” he stressed, “you can’t possibly begin to do something like this if you don’t have a value system in place that allows you to map concepts of ethics, beauty, and aesthetics onto our own existence.
“We need to understand the ways in which those things matter to us because these are powerful choices. Think about what happens when you really can print the genome of your offspring. You could start with your own sequence, of course, and mash it up with your partner, or as many partners as you like. Because computers won’t care. And if you wanted evolution you can include random number generators” which would have the effect of introducing the element of chance into synthetic design.
I wondered how much of this was science fiction, and how much was genuinely likely to happen. Endy stood up. “Can I show you something?” he asked as he walked over to a bookshelf and grabbed four gray bottles. Each contained about half a cup of sugar and had a letter on it: A, T, C, or G, for the four nucleotides in our DNA. “You can buy jars of these chemicals that are derived from sugarcane,” he said. “And they end up being the four bases of DNA in a form that can be readily assembled. You hook the bottles up to a machine, and into the machine comes information from a computer, a sequence of DNA—like TAATAGCAA. You program in whatever you want to build and that machine will stitch the genetic material together from scratch. This is the recipe: you take information and the raw chemicals and compile genetic material. Just sit down at your laptop and type the letters and out comes your organism.”
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