Synthesis of Horsepox from Mail-Order DNA

On July 6, 2017, Science magazine reported the results of an unpublished study in which Canadian researchers recreated an apparently extinct virus—horsepox, a virus related to smallpox—from genetic fragments ordered through the mail. ¹ Northern Arizona University Professor Paul Keim, a well-known authority on anthrax, noted that this development is likely to “reignite a long-running debate about how much science should be regulated.” ¹ This debate was fueled in the past by the de novo re-creation of polio virus in 2002, ² the Spanish flu in 2005, ³ and SARS in 2008 (see summary in Tucker ⁴ ). This latest event is being interpreted as demonstrating that the synthesis of infectious smallpox in the laboratory would require only a small team of scientists with “little specialized knowledge” ¹ for as little as $100 000.

The “dual use” nature of such research has long been recognized. Tucker ⁴ noted that commercial gene synthesis companies began to recognize this even before the 9/11 and anthrax letters attacks in 2001. Various groupings of synthetic DNA supply companies have formed a number of organizations to jointly adopt biosecurity practices. For example, the International Gene Synthesis Consortium (IGSC), which represents about 80% of worldwide commercial gene synthesis, adopted a harmonized screening program to promote biosecurity in 2009. IGSC companies screen orders for synthetic gene sequences from regulated pathogen sequences and supply such sequences “only to researchers in government laboratories, universities, non-profit research institutions, or industrial laboratories demonstrably engaged in legitimate research.” ⁵ The US government also weighed in with guidance on a screening framework for providers of synthetic DNA in 2010. ⁶ Like the IGSC protocol, the Department of Health and Human Services (DHHS) guidance calls for screening both sequences and customers, with follow-up and more in-depth screening where deemed necessary. The DHHS guidance also recommends consultation with and reporting to government contacts when receiving suspicious orders. Tucker ⁴ pointed out, however, that voluntary screening is not necessarily a very effective means of ensuring compliance and that the industry groups and the US government need to engage companies worldwide. Finally, Tucker ⁴ noted that regulating commercial companies would, in the long run, leave an important gap: As in-house sequencing with bench-top equipment becomes more common, scientists are likely to rely less and less on commercial suppliers.

On the positive side, re-creation of horsepox may provide pathways to developing new and better vaccines and therapeutics. It may also provide clues to the confused evolutionary picture for pox viruses. Although the smallpox (Variola virus) vaccine produced by Edward Jenner in 1796 was ostensibly based on cowpox (Vaccinia virus), the horsepox genome is said to look very much like old strains of vaccinia, ¹ strengthening a hypothesis that the vaccine was in fact derived from horses, not cows, and both of these may have originated as rodent pox viruses.

David Evans, leader of the Canadian virology team that recreated horsepox at the University of Alberta, says that he did the work to silence the debate on whether the recreation of pox viruses is feasible. Kupferschmidt ¹ quotes Evans as saying, “The world just needs to accept the fact that you can do this and now we have to figure out what is the best strategy for dealing with that.”

This development may revive not only the Dual Use Research of Concern (DURC) debate^7,8, but also serves to remind us that biosafety personnel at universities, government labs, and other research entities may have an increasingly important role to play in the future. This research illustrates the importance of Institutional Biosafety Committees (IBCs) conducting robust screening to identify and balance the benefits and risks associated with legitimate research that raises questions associated with DURC. As synthetic biology and gene editing technology advance and become more refined and efficient, it is likely that more research proposals will require examination by well-informed IBCs and perhaps will merit the inclusion of outside experts.