Smallpox: A New Kind of Computer Virus?

Source: Jan Bajtlik, New York Times

In 1975, smallpox was eradicated. Our war against one of humankind's greatest killers, with an estimated death toll of one billion people, was over. Humanity had won. There have been no cases of naturally occurring smallpox in almost four decades. 

And yet, as a New York Times op-ed argues, smallpox is just a mouse-click away. What could stop someone from searching up the genome and sending it out for synthesis? Scientists have it even easier; with the right machines, they could synthesize it from the comfort of their lab. Could inserting this synthetic genome into a human cell produce infectious virions?

Leonard Adleman, the op-ed author, says yes. He cites a 2002 study done by Cello, Paul and Wimmer at State University of New York at Stony Brook. In it, they succeeded in synthesizing a poliovirus genome from scratch and showing its moderate infectivity in mice. 

However, this is poor evidence that infectious smallpox could also be created in this way. First of all, poliovirus has a small RNA genome that is about 7,500 base pairs long. Smallpox has one of the largest DNA genomes, clocking in at around 200,000 base pairs. That alone is telling. Especially given the limitations of chemical DNA/RNA synthesis. Even for the small poliovirus genome, only small portions of it could be synthesized at a time. All of these short fragments would then have to be connected in the correct order. With a 200,000 bp long genome, that task would be herculean. 

Additionally, the smallpox DNA cannot infect cells all by its lonesome. It is a huge virus that carries with it many of the proteins it needs for replication and other functions. Without those, it cannot effectively propagate. Could the proteins be translated from the genome or also chemically synthesized? Perhaps. But that would be another major obstacle to overcome before creating a fully infectious smallpox virus. 

These two considerations alone severely undermine the validity of this op-ed's dire warning. Although there may be potential for bioterrorism from an adequately equipped lab and open-source infectious disease databases, especially with other viruses, the resurrection of smallpox is not on the horizon. 

References

1. http://www.nytimes.com/2014/10/16/opinion/resurrecting-smallpox-easier-than-you-think.html?_r=1
2. http://www.sciencemag.org/content/297/5583/1016.full
3. Knipe, D. M. & Howley, P. M. (Eds.). (2013). Fields Virology (6th ed.). Philadelphia, PA: Lipincott Williams & Wilkins. Accessed via OvidSP through Stanford.

Tina Ju