Proposed U.S. Guidelines on Synthetic DNA Balance Reward and Risk, Experts Say at AAAS

A proposed set of federal guidelines designed to sharply limit terrorists’ and criminals’ access to synthetic DNA would largely achieve security goals without harming research, experts said at a day-long discussion at AAAS. But a few experts at the meeting suggested that tightening and fine-tuning the tools and lists used for sequence and customer screening could make them more effective.

Gerald Epstein

To minimize the risk that manufactured DNA could be used to create harmful agents used for bioterrorism, the emerging sector of synthetic gene manufacturers are already screening potential customers and the gene sequences they request as proposed last fall by the U.S. Department of Health and Human Services (HHS).

Some questions emerged during the AAAS meeting over whether the screening methods could be tightened. Overall, however, there was wide support for the basic principles and voluntary guidelines set forth by HHS. While some speakers noted that no guidelines could eliminate risk, most agreed that the HHS framework would establish clear protocols that are strong and flexible enough to evolve with the emerging field.

“Stakeholders from academia, private industry, and the gene-synthesis industry all support the voluntary guidance,” concluded a meeting summary prepared by the staff of the AAAS Center for Science, Technology and Security Policy. “Although meeting participants identified specific concerns and offered specific recommendations to address some of those concerns, the overall sentiment was that the guidance is well thought out, facilitates advances in scientific knowledge, and allows for international engagement.”

The HHS guidelines—Screening Framework Guidance for Synthetic Double-Stranded DNA Providers—were issued in late November. They remind DNA producers of their requirements under current federal regulations and propose voluntary procedures that could be used to evaluate and screen both potential customers for manufactured genes and the gene products they might request.

Following the release of the screening framework, the U.S. Department of State joined HHS in requesting that AAAS convene a meeting of stakeholders to informally evaluate the proposed recommendations. That meeting, held on 11 January, was organized by Gerald Epstein, director of the AAAS Center for Science, Technology and Security Policy, and Kavita Berger, senior project director for biosecurity at the Center.

Nearly a hundred researchers, industry representatives and policy experts from government, private industry and non-governmental organizations visited AAAS headquarters in Washington, D.C., to discuss the plan in detail, with another 50 participating via webcast. Their discussion, summarized in the 23 January summary report, was submitted to the federal government and will be considered as the draft of the Screening Framework is revised.

Dramatic advances in synthetic gene production have drawn increasing interest from security and science policy experts. The field taps the skills of biologists, chemists, engineers, and computer modelers; they’re currently able to stitch together pieces of synthetic DNA—without the use of existing genetic material—to generate the genomes of small microbes. Within the past decade, researchers have used this technology to re-create infectious viruses such as polio, the virus implicated in the 1918 global flu pandemic, and SARS.

Such advances “drive cutting-edge research and novel solutions for practical application in medicine, energy production, agriculture, and other areas,” says the AAAS summary report released 23 January. “While advancements in genetic engineering and synthesis could help strengthen our response against infectious disease outbreaks, they could also be misapplied to evade a security regime that limits physical access to dangerous pathogens. The ability to synthesize genomes also raises concerns about the degree to which novel organisms might be created that had unpredictable properties.”

Epstein opened the meeting by noting that such discussions are crucial to support effective policy for powerful emerging technologies. “The ability to synthesize double-stranded DNA as well as the emergence of a set of firms that will provide that on order make this a much more salient policy issue” than it was in the early years of genomic research,” he said. “While the potential of the science has only begun to emerge, he added, “the question… is: Five years from now, what will we wish we had done today?”

That question is implicit as well in the HHS’s Screening Framework. It calls synthetic biology “the next significant transforming technology for the life sciences and beyond.”

The Framework recommends that when any potential customer requests synthetic double-stranded DNA that is 200 base pairs or greater in length (the human genome is 3 billion base pairs in length) the manufacturer would initiate screening. The process could clear the way for the sale—or, in cases where concerns about the client or the particular DNA sequence ordered can’t be resolved, it could lead to follow-up actions with the FBI or another government agency.

During the discussion at AAAS, panels broke the Framework into its components and examined each component for possible issues. And while the panel members were generally satisfied with the HHS proposal, they did register substantive concerns.

Some questioned the decision to set the bar for screenings at 200 base pairs, rather than look at even smaller DNA sequences which could, perhaps, be purchased from a provider and then built into a pathogen.

Because the field of synthetic DNA evolves so rapidly, it would be difficult to create a comprehensive database of genetic sequences that can potentially be used for harmful purposes; the Framework suggests a “best match” screening in which the ordered synthetic DNA is flagged based on its similarity to known “select agents,” or biological agents and toxins that could pose a severe threat to public, animal, or plant health. But, some asked, couldn’t an unknown sequence fail to make a close match with any known select agent and yet still prove dangerous?

And, others asked, with knowledge of DNA synthesis spreading, exactly who would monitor the field to make sure that the voluntary Framework protocols were achieving the intended goal?

“Synthetic biology has now moved outside the traditional academic research institutions,” said Dr. Harvey Rubin, an infectious diseases specialist who directs the Institute for Strategic Threat Analysis and Response at the University of Pennsylvania. “So the question of who does the regulatory body oversee is a really difficult one.”

Indeed, it is an international question—Germany and China are also emerging centers of synthetic DNA production. Science diplomacy has been and will continue to be essential for building common understanding and standards for production and sale of synthetic DNA, speakers said.

“The science is global…. it’s advancing rapidly in a number of laboratories around the world,” said Robert P. Mikulak, director of the Office of Chemical and Biological Weapons Threat Reduction at the Department of State’s the Bureau of International Security and Non-Proliferation.

Noting that “gene foundries” are operating in many nations, Mikulak added: “Whatever we do domestically, if we only do it domestically, it doesn’t really address the problem. We need a consistent approach globally, an approach that is not only adopted by the U.S. government and U.S. companies, but by companies in Germany, companies in China, companies in a number of other places as well.” Already, he said, the State Department has had “very positive consultations” on the issue with Germany.

Within the realm of conventional business and research institutions, the evidence thus far suggests that those who work with and sell synthetic genes are committed to a high standard of screening and other security measures, speakers said.

Private sector businesses have “every incentive to follow these guidelines and to insist they’ll only work w/ companies that do,” said Joseph Kittle, chairman of the Synthetic Biology Industry Association.” Not all companies are necessarily in compliance right now, but they’re all very close.”

They see it as “a matter of survival,” said Kittle. The concern is that should self-regulation prove insufficient, government could step in to do the oversight. In addition, he said, major customers in the private and public sectors have strong safety guidelines in place for the use of biological materials and are, by their nature, very risk-averse.

Leaders in the synthetic biology community “have definitely expressed concern that one thing is going to go wrong and that thing is going to shut down the industry completely,” said Michele Garfinkel, whose research at the J. Craig Venter Institute focuses on emerging societal concerns associated with new discoveries in genomics.

Such concerns signal a significant underlying tension within any effort to craft policy on synthetic double-stranded DNA: The need to assure security as much as possible while encumbering research and commerce as little as possible.

In Mikulak’s view, each of those are security issues.

“There’s the obvious concern… of the misuse of double-stranded DNA products for bioterrorism,” he said. But “the contributions that this kind of technology can make to strengthening our defenses against infectious disease, that’s also a security issue, whether the disease is naturally occurring or whether it’s deliberately spread. This kind of technology—if it were not allowed to advance rapidly, that would really hamper our efforts to build a public health system and bio-defense preparedness.”

Though questions remain on whether the HHS Framework will be strong enough, Epstein noted that considerable pressures are built-in even to a voluntary regime.

“I would hope that if there were any significant number of firms—or even one or two that were consciously defying the guidance and trying to be a ‘gray market’ or black market provider—I would expect those firms that are complying with the guidance would be the first ones to notice,” he said. “We’re hoping there’s some value in shaming the firms that are not doing it (compliance)…

“Lets’ say the firms are overseas and you know that you have to go to firm x in country y to get your shady DNA—I would just suggest that U.S. intelligence agencies may be interested to see what that firm is really up to.”

Still, several speakers acknowledged that no system of screening—voluntary or otherwise—will be perfect. One drew comparisons between the HHS proposal and a bullet-proof vest: It will protect your core, but there are still vulnerabilities.

The Framework would allow “reasonable” ability to assess how companies are screening potential customers, Epstein said. But, he added, “the thing we’re going to have a very hard time measuring is how many terrorists we stopped. I would like to hold out that we can’t really measure the thing we really care about, and we’re just going to have to live with that.”

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