DNA SYNTHESIS:
Gene-Synthesis Companies Join Forces to Self-Regulate
Yudhijit Bhattacharjee
In 2004, Blue Heron Bio, a gene-synthesis company in Seattle, Washington, received a request by someone in the United States for a DNA sequence that would help a gene produce a toxin more effectively in an edible plant. Another order that year, by an organization in the Middle East, was for a part of the smallpox genome. Afraid that the DNA might fall into the hands of terrorists, the company declined both requests.
But it didn't have to. Existing laws in the United States, as well as most other countries, do not require companies to screen DNA orders, let alone turn down suspicious requests or report them to any government or body such as the United Nations.

Now, Blue Heron Bio and a host of other gene-synthesis companies have proposed guidelines for screening and handling the growing number of DNA orders. Founding members of the International Consortium for Polynucleotide Synthesis (ICPS) lay out the oversight framework in a commentary published this month in Nature Biotechnology. "We think this is a sensible way of handling the risks without slowing down the field," says co-author John Mulligan, chair of Blue Heron Bio.

Environmental activists are bristling at the proposal, which they say is an attempt by industry to preempt or minimize government regulation. The absence of formal oversight, they claim, makes the rapidly advancing field of synthetic biology a fertile ground for bio-terrorism as well as ecologically catastrophic accidents. "It's not for a handful of scientists and entrepreneurs who have a vested interest in the technology to control the discourse or determine regulatory frameworks," says Hope Shand, research director of the ETC Group.

The topic is sure to provoke debate next week in Zurich at Synthetic Biology 3.0, the third in a series of meetings that brings scientists together to discuss technical, societal, and ethical issues related to the field. Even a coauthor of the ICPS framework rejects its plea for governments to stay on the sidelines. Harvard University biologist George Church, a co-founder of Cambridge-based gene synthesis company Codon Devices, says he recommends government surveillance of companies, institutions, and researchers doing synthetic biology "since the stakes are so high."

At last year's Synthetic Biology 2.0, Church and other biologists publicly discussed security implications of their research, and some even raised the idea of a moratorium. But after a contentious debate, meeting participants issued only a vague call for self-regulation that infuriated the ETC Group and other watchdog groups (Science, 26 May 2006, p. 1116).

Under ICPS's proposal, customers placing orders would identify themselves and their home institutions and provide information about their capability to handle biological agents. Companies would be obligated to use industry-approved software to check orders against a list of potentially dangerous sequences and report problematic requests to government authorities. Founding members of the consortium say they already follow these steps.

So far, the push for self-regulation among synthetic biology researchers and companies has warded off government involvement. Neither the U.S. Department of Homeland Security nor any members of the U.S. Congress have called for binding legislation over the field. Some government officials have pointed out that the country's select-agent rules, which require individuals and institutions to register with the government in order to work with certain pathogens and toxins, already exert indirect pressure on gene-synthesis companies to screen orders.

The National Science Advisory Board for Biosecurity (NSABB), a panel appointed by the Department of Health and Human Services to minimize risks posed by "dual-use" life sciences research, has endorsed self-governance. In draft recommendations on synthetic biology unveiled earlier this year, the board suggested developing standards for screening DNA orders but didn't suggest new regulations (Science, 27 April, p. 529). If the government were to get tough in this area, "it could drive business overseas," says David Relman of Stanford University in Palo Alto, California, who heads NSABB's synthetic biology group.

Although praising the ICPS consortium for trying to address the risks posed by synthetic biology, some are troubled by the lack of regulatory teeth in the framework. Alan Pearson of the Center for Arms Control and Non-Proliferation in Washington, D.C., asks who would hold DNA-synthesis companies and their clients accountable if they ignored the guidelines. Pearson is surprised that the consortium did not recommend modifying the select-agent rules to cover requests for and manufacture of DNA sequences related to such agents.

The paper dismisses another obvious idea: a centralized government body that clears all DNA orders. That "impractical option," say the authors, would scare off clients concerned about breach of privacy. "Most of our customers are very concerned about protecting the confidentiality of the sequences they are ordering, which are often highly proprietary," says Mulligan.

Church stresses the need to develop better software to screen DNA requests. Industry representatives say the number of false alarms they have to look into makes the process tedious. "No matter what the regulations, good software is our first line of defense," says Church, adding that the consortium plans to pool resources and request government funding to improve screening.

Although Church contends that self-governance is not enough, his voice wasn't enough to persuade the ICPS that government regulation is needed or feasible. "I think it would take a significant change in the culture of science and business to support broad-scale surveillance of DNA sequences that people work on," says Mulligan. "I think it would be a difficult change to make."