Living Legos

Benjamin, I have one word for you: syntheticbiology. Of course, there is no need to update The Graduate, and that is really two words, but rewriting that line is a national pastime, and if we can string together small stretches of DNA to create a new organism, why fret over mashing a few words together.

Synthetic biology is not new. Scientists have been piecing together short stretches of DNA for decades. But as a recent report points out, advances in the speed with which DNA can be assembled and the growth of a commercial industry that produces short and not-so-short strands of DNA compel us to confront the implications of this technology becoming available to a much larger number of people. Synthetic Genomics: Options for Governance (www.jcvi.org/research/synthetic-genomics-report/) provides a thoughtful and useful framework for finding a path that will make it possible to tap the spectacular potential for useful applications of this technology while protecting society from its accidental and deliberate misuse.

Although the report was prepared by the J. Craig Venter Institute, the Center for Strategic & International Studies, and MIT, its deeper heritage is the dearly departed Office of Technology Assessment. Several of the authors and core advisory group members are OTA veterans, and the analysis is quite explicit in its intention to follow the OTA practice of presenting options, not recommendations. But borrowing a page from Consumer Reports, the report includes a chart in which the options are evaluated for their likely effectiveness with a range that extends from solid circles for Lexus-like dependability to empty circles for the policy equivalent of your father’s Oldsmobile.

Progress in the field has reached a pace that would make Gordon Moore’s head spin. In the early 1970s, Har Gobind Khorana with a team of 17 colleagues spent years assembling a gene with 207 base-pairs. In the 1990s, a large team with plenty of time could assemble a gene with 2,700 base pairs. In 2002, a team led by Eckard Wimmer spent about a year assembling an infectious poliovirus with 7,400 base-pairs directly from nucleic acids. A year later a Venter Institute group constructed a virus with 5,400 base-pairs, but it took only two weeks. Today, 24 U.S. firms and an additional 21 across the globe are building and selling segments of DNA as long as 52,000 base-pairs.

What once took a team of top scientists years to achieve can now be ordered with a phone call. And the stretches of DNA that are purchased can be cobbled together in a variety of ways using commonly available laboratory equipment. It’s not quite as simple as Legos yet, but one can readily imagine a day when amateurs could assemble genes in their garages. Perhaps the thought of alienated young gene hackers and retired boomers experimenting with new life forms does not lift your spirits. If not, don’t even start to think about how a terrorist might use this capability.

So maybe it’s time to think about how to govern this technology. Is there a way to enjoy the new medicines, materials, and sustainable transportation fuels that might become realities through synthetic biology without living in fear of environmental disasters or planned epidemics?

The work has already begun. The National Academies have issued several reports that touch on this question, and their Committee on Science, Technology, and Law is planning a workshop on the subject in 2008. The Department of Energy’s Biological and Environmental Research Advisory Committee recommended action, and a group at the University of California at Berkeley proposed voluntary steps the research community should take. Participants in the international Synthetic Biology 2.0 conference called for addressing security concerns, and the industry association of firms that produce and sell DNA segments is exploring what the companies should do to screen orders to ensure that they know when they are being asked to synthesize DNA from a dangerous pathogen.

As the Synthetic Genomics report explains, the broad range of concerns that should be addressed include “cultural and ethical concerns about manipulating life, economic implications for developed and developing regions, issues related to ownership and intellectual property, concerns about environmental degradation, and potential military uses.” But since the September 11, 2001, terrorist attacks, the prospect of terrorists developing and releasing a virus or other biological weapon has generated the most intense anxiety.

The report finds that the construction of a virus through synthetic biology is still so difficult that it is not a terrorist threat today. Looking ahead, the report concluded that “Over the next five years constructing an infectious virus will remain more difficult than obtaining it from nature or from laboratory stocks, with a few important exceptions [smallpox, ebola/Marburg, 1918 flu, and foot-and-mouth disease]. In ten years, however, the situation might be reversed.” Now is the time to begin preparing safeguards that will make this possibility less likely.

The report focuses on three areas of concern: enhancing biosecurity to protect against terrorists, fostering laboratory safety to safeguard lab workers and nearby communities, and protecting the environment. This is a good beginning, but as the report acknowledges there will be numerous other issues to address: government-supported R&D activities over which the United States has no control, ethical questions, related general biotechnology topics, and the adequacy of public health systems to deal with an accident or attack, to name a few.

But if you are wondering if it is worth opening this can of worms, consider the even more mind-boggling list of possible benefits. Synthetic genomics will open innumerable pathways for basic genetics research. Vaccine development and production could become much more efficient with the ability to make subtle DNA-level changes. Indeed, synthetic biology could make an enormous difference in all drug development and manufacturing. It could play a vital role in developing a cost-effective means to produce cellulosic ethanol and in manufacturing alternatives to many petroleum-based products. Fittingly, it might make it possible to replace the plastics that Benjamin was originally advised to pursue.

Science and technology policy sometimes seems mired in a Mobius strip. Debates about nuclear weapons, science and math education, evidence-based medicine, the role of government in applied research, and new energy technologies can make one feel condemned to an existential hell of reruns. Synthetic biology, for good and ill, offers something new. Although it raises some profound and long-discussed questions about human hubris, it also opens the door to a new world of potential risks and benefits. Now is the time to roll up our sleeves and get to work.