Preparing the World for Synthetic Biology

Synthetic biology has come a long way in the last two years. It is no longer dismissed as just another overhyped offshoot of the Human Genome Project, but rather is recognized as a transforming technology that will change the way we generate energy and manufacture medicines, materials, and computers. The field has earned the attention of researchers and policymakers, the financial support of venture capitalists, NASA, and the Pentagon, ink from magazines like Scientific American, and the dedication of an MIT biological-engineering professor named Drew Endy. Drew who? Who, indeed. Despite competing for airtime with world-renowned researchers like George Poste and Craig Venter, Endy has become a thought leader in a field that needs all the deep thinkers it can find.

Synthetic biology is the quest to design and build, one gene at a time, organisms that do things that organisms made by Mother Nature cannot. There are many applications for synthetic biology, but the ones of most interest, according to Endy, involve the life sciences, energy, materials science, and information technology.

Unlike most scientists and engineers, Endy has to worry about the public acceptance of his field. Its goal, after all, is to transform biology from a science into an engineering platform—complete with an instruction manual and a standardized list of parts and assembly procedures—that industries can one day use for the design, manufacture, and testing of products. In some cases, this platform will rely upon insights gained from creating and taking apart synthetic organisms. Endy wants the public to understand that these organisms will not take the form of three-headed monkeys running in the streets, or transgenic pollens drifting into wheat fields. They will be, in many cases, single-cell organisms that can live only a few hours, and only in a petri dish or a test tube.

But there are legitimate concerns about the safety and ethics of synthetic biology. Unlike the genetic engineering that produces pesticide or herbicide resistance in plants, or human therapeutic proteins in the milk of goats, synthetic biology represents the ability to construct vastly more powerful and problematic organisms from scratch. In July 2002, researchers at the State University of New York announced that they had synthesized the deadly and virulent polio virus. This event, which was criticized by scientists and ethicists alike, marked the first time an organism was created entirely from off-the-shelf materials and instructions. SUNY researchers say they did it to illustrate just how easy it is for scientists to construct life—and for would-be terrorists to construct bioweapons. Synthetic biology also represents the ability to construct artificial life forms that are not modeled on anything found in nature, and whose benefits and hazards are consequently only theoretical. There is no bioethical road map for constructing synthetic organisms one gene at a time.

“We’re talking about engineering biological systems and organisms,” says Endy. “There is a risk that somebody will find a way to use this technology to cause harm, and there will be questions about whether this is ethical and truly useful to society or just all about scientific glory and corporate profit. I don’t think it is, but how do those of us in the field help get the public from a place of fear and mistrust to a place of trust and acceptance? How do you get from here to there? There is a lot at stake.” Endy, who is creating a library of standardized interchangeable genes, is also helping to ensure that his colleagues recognize the ethical implications of their work. Last summer, he helped organize the first synthetic-biology conference, held at MIT, and he continues to speak out about the dilemmas the emerging field poses for scientists.

Building the Foundation
With the Synthetic Biology 1.0 conference, the field took a giant step forward. For the first time, practitioners gathered under one roof to share their data and dreams with each other—and with some interested parties from government and the investment community. Endy used his platform as one of the organizers and speakers to push the point that while data and good intentions are fine, the success of synthetic biology requires something more. What will be needed, he said, is a foundation built from a sturdy matrix of organizing principles, transparency, public education, and a strategy for dealing with the media, IP lawyers, investors, and entrepreneurs the field will attract. It was a bold, perhaps premature, call to arms.

Endy reasons that if you’ve got people like Poste talking about how important and potentially widespread synthetic biology could become—in good ways and bad—it’s time for the rest of the field to start talking about it too.

“A lot of people have their heads in the sand, or up in the clouds, about this issue. I don’t know if we need an Asilomar Conference,” says Endy, referring to the 1975 conference where the ethics and guiding principles for working with recombinant DNA were debated and delineated, paving the way for the biotech industry as we know it. “But I do know that it’s not too early to start talking about these things.”

Endy has already backed up his lofty talk. He has agreed to help craft and coördinate efforts in the synthetic-biology community to define ethical conduct and establish guiding principles. He will report on the progress of these efforts at Synthetic Biology 2.0, which will be hosted this year by the University of California, Berkeley. He also says he is willing, if asked, to meet with schools, regulators, and even politicians to address concerns about the dangers of synthetic biology.

Brick Library
Synthetic biology has been around for decades. The transgenic engineering debated at Asilomar was, in a sense, a rudimentary form of synthetic biology. But it wasn’t until 2003 that the field began to heat up. It was in the fall of that year that genome-sequencing maverick J. Craig Venter announced that he had produced a synthetic, self-replicating virus in just two weeks. Venter is trying to design a simple microörganism capable of consuming unnaturally large amounts of carbon dioxide. The goal: a self-replicating pollution-filtration system that never needs replacing or new sources of fuel.

Also in 2003, NASA Astrobiology Institute researchers corroborated the notion that synthetic biology might help the search for signs of life on Mars.

The same year marked the first time that an artificial genetic system constructed from a six-letter genetic alphabet—the natural genetic alphabet has only four letters—yielded a normal polymerase chain reaction, a process in which bits of DNA are copied, producing more bits of DNA that can themselves produce even more bits of DNA. This advance paves the way toward a library of artificial genes that mimic natural and engineered gene function.

For their part, Endy and colleagues have started building a library of what they call “biobricks.” Like most of his work, Endy’s library is in the public domain so that scientists and students can browse through it to see what kinds of novel biological systems they can create, either by design or by serendipity. Biobricks are prominent among the materials nudging synthetic biology toward the engineering disciplines, because they allow for a framework of standardized parts and systems.

Little wonder that the biotech industry is keeping tabs on Endy. “He is certainly one of the leaders in this field who everybody wants to talk to now,” says Brent Erickson, vice president of the industrial and environmental division at the Biotechnology Industry Organization, the leading trade group in the biotech field.

But Endy’s willingness to wrestle with the ethical and societal conundrums of synthetic biology earns as much respect as his technical accomplishments. “I think a lot of scientists and industry folks say they get it, but I’m not sure they know what to do about it,” says John Mulligan, CEO and founder of Blue Heron Biotechnology, a firm that synthesizes genes and DNA sequences. “Drew does.”

Mind the gap
Indeed, few scientists have the stomach to engage the public and the media as Endy has. Ortwin Renn of the University of Stuttgart noted at last summer’s EuroScience Open Forum in Stockholm, Sweden, that scientists are often deeply scornful of those who do. “They view it as a PR stunt,” he says.

Endy says that a well-respected professor approached him after the Synthetic Biology 1.0 conference, wondering whether researchers were “shooting ourselves in the foot” by raising concerns prematurely. After all, synthetic biologists were still far from creating any potentially harmful applications, and discussing what to do about them could set off false alarms.

Reflecting on the encounter, Endy shrugs. “What people need to understand is that we don’t have the answers to some key questions, like, What are the most useful and beneficial applications? Who is going to control the IP? Who is going to make sure it is not abused? How do we even begin to start educating the public about the risks and rewards?”

If there are answers to these questions, Drew Endy aims to find them. “I really want to see how far this field can go,” he says. “The answer is ‘Not very far’ if we can’t figure out how to get from here to there.”