Expert Report

Sequence-Based Classification of Select Agents: A Brighter Line (2010)

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Although measures are in place to protect against the loss, theft, or misuse of Select Agents—a list of the names of pathogens or biological toxins with the potential to pose a severe threat to public health and safety—concerns are growing that advances in molecular biology have created new biosecurity challenges. In particular, DNA synthesis technology may make it possible to create Select Agents, modify them by introducing small changes to the genetic sequence, or to construct entirely novel pathogens. This report considers the scientific advances necessary to develop an oversight system for synthesized Select Agents and novel pathogens based on the predicted features and properties of the genes encoded by their DNA.

Key Messages

  • A sequence-based classification system for Select Agents could be developed using current technologies. This system would define Select Agents in terms of DNA sequence rather than taxonomic names, in order to better define what is subject to Select Agent regulations; thus establishing a brighter line.
  • A sequence-based prediction system for oversight of Select Agents is not possible now or in the near future. Firstly, Select Agent status depends on characteristics that are not encoded in an organism's genome sequence, such as the economic factors or public perception, and therefore it is not feasible to predict Select Agent status from genome sequence alone. Secondly, identifying the biological properties of a dangerous pathogen from gene sequence is an extraordinarily difficult problem, requiring a deep understanding of the interaction of the complete pathogen and its host in the environment—a level of understanding that is currently beyond the realm of possibility.
  • A yellow-flag system would work with sequence-based classification to flag sequences of concern. These might be fragments of genetic sequences or suspicious sequences that might encode potentially hazardous genes, yet are not themselves Select Agents. Upon identification of such a sequence, a yellow flag would be raised triggering a common-sense follow-up; for example, a DNA synthesis company may contact a customer to ensure that they know they have just ordered a sequence that could be considered dangerous, or pass the details of the order on to law enforcement authorities.
  • Abilities to predict pathogenicity from genome sequence and to design novel pathogens are linked. Prediction is currently unfeasible, and therefore the threat of using synthetic biology to design entirely novel pathogens is also improbable—the designer would not be able to predict from sequence if the designed sequence would have pathogenic properties.
  • Near-term milestones for sequence-based classification include: A sequence database with a Select Agent focus; an expanding sequence database of all biology; defining the criteria for Select Agent designation; and stratifying the Select Agent list based on risk.
  • Recent years have brought rapid advances in biotechnology with clear benefits to humankind—but also the potential that these advances may be used for nefarious purposes. Of particular concern are the pathogens or biological toxins known as Select Agents, identified as those posing the greatest threat to public health and safety.