Want to create a pathogen? Just download its gene sequence information from the Internet and place an order with a gene sequencing company. The genes arrive in the mail a couple of days later. Mix it in your basement lab and then release on an unprotected public. Is this nightmarish vision of mail-order bioterrorism really possible?
Most experts agree that basement bioterrorism is unlikely right now. But rapid improvements in the technologies that allow researchers to generate genetic material starting from just information and raw chemicals could make such bioterror attacks possible in the next decade or so. The synthesis of entire viral genomes—the complete set of genetic information of these microbes—has already been done by legitimate researchers.
For example, in 2002 one team constructed the polio virus using only published DNA sequence information and mail-ordered raw materials. In 2005, another group similarly reconstituted the 1918 pandemic influenza virus that killed tens of millions of people.
DNA synthesis is now a billion dollar business. Currently there are at least 25 companies in the U.S. and 21 others around the world that are capable of manufacturing gene-length stretches of DNA. And the cost and ease of gene synthesis has fallen more than 50-fold and is halving every 32 months. In addition, 15 firms in the United States and seven foreign companies sell new or refurbished DNA synthesizers. Tens of thousands of these machines have been manufactured and are widely available. Used ones have been offered eBay.
The burgeoning field of synthetic genomics promises vast new possibilities for curing disease and producing new eco-friendly products and services. However, like all technologies, synthetic genomics can be abused. In June, this concern was addressed by researchers in an article in Nature Biotechnology, "DNA synthesis and biological security." The researchers made three broad recommendations, i.e., researchers ordering synthesized DNA must identify themselves and their institutions to the companies from which they are ordering sequences; companies should use software to screen orders for suspect sequences; and sequence manufacturing companies should work with government agencies to establish a system for alerting officials to suspect behavior.
The researchers also highlighted proposals that they believed would be impractical. These included limiting access to material, equipment and know-how; restricting access to information about pathogenic DNA sequences; and, checking all DNA sequence orders through a centralized government clearinghouse.
In October, a private initiative by the J. Craig Venter Institute, a Washington, D.C.-based think tank, the Center Strategic and International Studies and the Massachusetts Institute of Technology released a new report specifically focusing on the dual-use concerns of synthetic genomics, i.e., the construction of functional organisms at the lab bench from scratch. The report, Synthetic Genomics: Options for Governance (Venter Report) aims at preferred policy solutions that "both minimize the risks from nefarious uses and minimize the impediments to beneficial uses of the technology."
How fast do researchers and policymakers need to move to prevent synthetic genomics from being abused? The good news is that the best judgment of the researchers is that synthesizing pathogens like the smallpox virus is still too complicated for would-be bioterrorists. For the near-term, bioterrorists are more likely acquire pathogens the old-fashioned way, by stealing them from labs or isolating them from the wild. However, the report takes "as a given that now, or within a few years, any virus with a known sequence can or will be able to be constructed in a relatively straightforward manner."
The Venter Report researchers identified three major points for policy intervention; commercial firms that sell synthetic DNA; owners of bench-top DNA synthesizers that can make their own DNA; and, researchers who use of synthetic DNA themselves.
At the point of DNA synthesis, the researchers suggest that all DNA synthesis companies use software to screen orders for suspect sequences. Such suspect sequences can be found in databases such as the Lawrence Livermore National Laboratory's virulence factor database and the National Select Agent Registry. The majority of sequence manufacturing companies already do this, so it should not be a problem to extend this requirement to the remaining companies.
Another possible safeguard would require that institutional biosafety officers certify to DNA synthesis firms that the people ordering sequences are legitimate researchers. This would make the research institutions where scientists work rather than DNA synthesis firms responsible for verifying legitimate users. Once a scientist had been certified as a legitimate user, the biosafety officer wouldn't have to screen each shipment. In addition, a list of approved researchers could be maintained and updated electronically so that individual orders could be approved with minimal time delay. As the report notes, this is procedure is similar to the approach used by the American Type Culture Collection (ATCC) which distributes biological materials such as cell lines, bacteria, animal and plant viruses. The ATCC only ships potentially hazardous material with the approval of a registered biosafety professional.
One other suggestion aimed at sequencing companies is that they keep a record of who orders what for a specified amount of time. This information could be passed along to police officials in the event of an incident.
What about those bench-top DNA synthesizers with which researchers can make their own gene sequences? One suggestion is that the synthesizers should be registered with a government agency so that each has a known assigned owner. A more stringent requirement would be licensing synthesizer owners, that is, only people who are approved by the government beforehand may possess such machines. Discovering that a machine is either unregistered or unlicensed would be an immediate cause for suspicion. An even tougher constraint would be requiring that everyone who uses materials associated with producing gene sequences be licensed.
The last point of policy intervention discussed in the Venter Report is the consumers of synthetic DNA themselves: researchers. Here the report makes a number of reasonable suggestions with regard to educating researchers and establishing cultural norms. These include educating young researchers about risks and best practices as part of university curricula; compiling a manual for biosafety in synthetic biology laboratories; and, establishing a clearinghouse for best practices. The report also suggests broadening Institutional Biosafety Committee (IBC) review responsibilities to consider risky experiments. IBCs exist at most research institutions though small private companies may have to seek outside evaluation of biosafety issues.
The IBCs could initially use the criterion established in the National Academy of Sciences' (NAS) 2004 report, Biotechnology Research in the Age of Terrorism to identify experiments that merit extra scrutiny. The NAS report named seven classes of risky experiments. Specifically, experiments that (1) demonstrate how to render a vaccine ineffective; (2) confer resistance to therapeutically useful drugs; (3) enhance the virulence of a pathogen or rendering a nonpathogen virulent; (4) increase transmissibility; (5) alter host range; (6) enable the evasion of a diagnostic or other detection; and (7) enable weaponization. Earlier this year, the National Scientific Advisory Board for Biosecurity (NSABB) issued a proposed framework for the oversight of dual-use life sciences research that expanded somewhat on the NAS list of risky experiments.