Photographs by Mark Ostow
George Church is an imposing figureover six feet tall, with a large, rectangular face bordered by a brown and silver nest of beard and topped by a thick mop of hair. Since the mid-1980s Church has played a pioneering role in the development of DNA sequencing, helpingamong his other achievementsto organize the Human Genome Project. To reach his office at Harvard Medical School, one enters a laboratory humming with many of the more than 50 graduate students and postdoctoral fellows over whom Church rules as director of the school's Center for Computational Genetics. Passing through an anteroom of assistants, I find Church at his desk, his back to me, hunched over a notebook computer that makes him look even larger than he is.
Church looms especially large these days because of his role as one of the most influential figures in synthetic biology, an ambitious and radical approach to genetic engineering that attempts to create novel biological entitieseverything from enzymes to cells and microbesby combining the expertise of biology and engineering. He and his lab are credited with many of the advances in harnessing and synthesizing DNA that now help other researchers modify microrganisms to create new fuels and medical treatments. When I ask Church to describe what tangible impact synthetic biology will have on everyday life, he leans back in his chair, clasps his hands behind his head, and says, "It will change everything. People are going to live healthier a lot longer because of synthetic biology. You can count on it."
Such grandiosity is not uncommon among the practitioners of synthetic biology. Ever since Church and a few other researchers began to combine biology and engineering a dozen years ago, they have promised it would "change everything." And no wonder. The very idea of synthetic biology is to purposefully engineer the DNA of living things so that they can accomplish tasks they don't carry out in nature. Although genetic engineering has been going on since the 1970s, a rapid drop in the cost of decoding and synthesizing DNA, combined with a vast increase in computer power and an influx into biology labs of engineers and computer scientists, has led to a fundamental change in how thoroughly and swiftly an organism's genetics can be modified. Church says the technology will eventually lead to all manner of breakthroughs: we will be able to replace diseased tissues and organs by reprogramming cells to make new ones, create novel microbes that efficiently secrete fuels and other chemicals, and fashion DNA switches that turn on the right genes inside a patient's cells to prevent arteries from getting clogged.
Even though some of these applications are years from reality, Church has a way of tossing off such predictions matter-of-factly. And it's easy to see why he's optimistic. The cost of both decoding DNA and synthesizing new DNA strands, he has calculated, is falling about five times as fast as computing power is increasing under Moore's Law, which has accurately predicted that chip performance will double roughly every two years. Those involved in synthetic biology, who often favor computer analogies, might say it's becoming exponentially easier to read from, and write into, the source code of life. These underlying technology trends, says Church, are leading to an explosion in experimentation of a sort that would have been inconceivable only a few years ago.
Up to now, it's proved stubbornly difficult to turn synthetic biology into a practical technology that can create products like cheap biofuels. Scientists have found that the "code of life" is far more complex and difficult to crack than anyone might have imagined a decade ago. What's more, while rewriting the code is easier than ever, getting it right isn't. Researchers and entrepreneurs have found ways to coax bacteria or yeast to make many useful compounds, but it has been difficult to optimize such processes so that the microbes produce significant quantities efficiently enough to compete with existing commercial products.
Church is characteristically undeterred. At 57, he has survived cancer and a heart attack, and he suffers from both dyslexia and narcolepsy; before I visited him, one of his colleagues warned that I shouldn't be surprised if he fell asleep on me. But he has founded or taken an advisory role in more than 50 startup companiesand he stayed awake throughout our time together, apparently excited to describe how his lab has found ways to take advantage of ultrafast sequencing and other tools to greatly speed up synthetic biology. Among its many projects, Church's lab has invented a technique for rapidly synthesizing multiple novel strings of DNA and introducing them simultaneously into a bacterial genome. In one experiment, researchers created four billion variants of E. coli in a single day. After three days, they found variants of the bacteria in which production of a desired chemical was increased fivefold.
The idea, Church explains, is to sort through the variations to find "an occasional hopeful monster, just as evolution has done for millions of years." By mimicking in lab experiments what takes eons in nature, he says, he is radically improving the odds of finding ways to make microbes not just do new things but do them efficiently.
A DNA Turn-On
In some ways, the difficulties researchers have faced making new, more useful life forms shouldn't come as a surprise. Indeed, a lesson of genome research over the last few decades is that no matter how elegantly compact the DNA code is, the biology it gives rise to is consistently more complex than anyone anticipated. When I began reporting the early days of gene discovery 30 years ago, biologists, as they often do, thought reductively. When they found a gene involved in disease, the discovery made headlines. Scientists said they believed that potent new medicines could soon deactivate malfunctioning versions of genes, or that gene therapy could be used to replace them with healthy versions in the body.
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Biology's Master Programmers
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