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Bioterror Threat from Gene Synth Is Immediate, Not Far-off


Thank you for your discussion of bioterrorism: “Terror by Oligo” in the January 2003 issue of Genome Technology. We believe it is an important topic and we know that the potential threat is immediate rather than futuristic.

Although it took Wimmer’s group three years to construct the 7,500 bp poliovirus, Blue Heron Biotechnology has synthesized, cloned, and sequence-verified genes of this size in less than 12 weeks. This demonstrates that the potential for bioterrorism using synthetic materials is present today rather than being 10 or 20 years off.

We have been proactive in managing the threat of bioterrorism from synthetic genes. In February 2001, we implemented an automated BLAST search against the Centers for Disease Control list of controlled pathogens ( In 2002, we became a beta site for Craic Computing to test the now-commercial BlackWatch program. BlackWatch provides convenient search tools and a database of pathogens that are controlled by the Centers for Disease Control, the Department of Commerce, and the United States Department of Agriculture (

Our customers submit their confidential sequences via a secure website. Inside our firewall, we use BlackWatch to conduct an automatic BLAST search that confidentially compares the customer sequence to pathogenic genomes (we do not search customer files against any other database, so aside from identifying pathogens, we do not know which genes we are synthesizing).

Since marketing our technology, Blue Heron has received quite a few synthesis requests for genes from controlled pathogens. The bulk of requests for synthesis of genes from Select Agents have originated from customers engaged in vaccine development, including those sponsored by the US government. To support counter-terrorism research on vaccines, we applied to the CDC and received certification to synthesize and transfer Select Agents.

Some inquiries, however, caused concern. For example, a prospective US customer requested our proprietary GeneMaker Codon Optimization to prepare cholera toxin for expression in an edible plant; we declined the order due to the potential safety issues. We also received a request to synthesize a variola gene (related to smallpox) from a laboratory in Saudi Arabia. Although this order may be legitimately related to vaccine development, we did not fulfill the request due to the potential risk and the additional regulatory requirements for international transfers (from the Department of Commerce and the equivalent authority in the recipient’s country). As a final example, we received an e-mail from an AOL account in Germany asking for a quote to synthesize a novel gene distantly related to HIV, which we chose not to synthesize.

The potential damage from bioterrorism warrants vigilance even if the likelihood of bioterrorism is low. Synthesis providers can easily and confidentially check requested sequences against pathogenic sequences by setting up an internal BLAST search. Such practices should be the industry standard to decrease the risk of bioterrorism and to demonstrate responsible business practices. Unfortunately, these measures cannot eliminate the risk of bioterrorism, but they may reduce it.

John Mulligan, PhD
President and CEO
Blue Heron Biotechnology


In GT’s January issue, data for a progress report showing how many products some of the main genomics-to-drugs companies have in their clinical pipeline was taken from the companies’ websites. Human Genome Sciences brought to GT’s attention that its website is not up to date. The correct numbers for HGS are: more than 30 products in preclinical, six in phase I, and two in phase II.


In the February issue of GT the size of Peter Coggins’ workforce was misstated in the cover story. His staff was doubled last year to 4,500.


Unless requested otherwise, any correspondence to Genome Technology may be published. Letters may be edited for length and clarity. Send mail to [email protected] or mail to
Editor, Genome Technology,
PO Box 998, Peck Slip Station,
New York, NY 10272-0998

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