Fifteen years ago a group led by Eckard Wimmer shocked the scientific community by announcing they had chemically synthesized viable polioviruses (1). Using the genomic sequence published online they were able to patch together DNA fragment analogs and debug errors to artificially recreate functional viruses. It took 3 years to complete this work.
That Was Yesterday
Science has come a long way since 2002. As genomes go, poliovirus is small and some experts noted synthesizing far more complex entities like smallpox using the Wimmer group method was simply not feasible (1). That was then. The technology has advanced to the point that horsepox, a virus believed to be extinct with a genome about 28 times larger than polioviruses, has been resurrected by chemical synthesis (2). This accomplishment suggests that the method could be adapted to synthesize its slightly smaller and deadly relative, smallpox virus. Whether through accident or deliberate action, release of smallpox could be disastrous.
In 2002 experts projected that improving DNA synthesis capabilities might eventually make it possible to re-create smallpox using a different approach. The simpler, alternative strategy would be to take a benign close relative like cowpox virus and systematically modify it to have the same genetic code as smallpox. Improvements to DNA synthesis and manipulation techniques have increased the capabilities of genetic engineers. What this means is that in 2017 there are two entirely feasible ways to cook up some smallpox.
A Surge of Developments
A convergence of scientific advancements has already yielded tools enabling scientists to create and alter genetic information with unprecedented speed and precision. Researchers and societies are now attempting to define if and when genetic manipulation technologies will be employed (3). Science has charged ahead so fast even scientists are unsure how to proceed. And proposals currently under development (4) will foster synergistic expansions in the ability to synthesize, manipulate and modify large DNA molecules. When these projects come to fruition they may make our current genomic engineering capacities seem primitive in comparison.
The polio-to-pox synthesis Odyssey demonstrates how fast speculative fancy turns into hard fact in scientific research. It also reveals how new developments shift the landscape of potential threats. Sequence database repositories have been critical for researchers for years. Today and going forward, as it becomes feasible for nefarious actors to use sequences as templates to synthesize pathogens, it may become necessary to evaluate what information should be restricted. Powerful technologies such as the CRISPR genetic editing tools are so broadly accessible and potentially applicable to so many situations it is impossible for experts to anticipate all the possibilities. As an example, Dr. Jennifer Doudna, an inventor of CRISPR technology, has described how she had a sudden revelation regarding the potential safety risks posed by modifying a virus to ferry specific DNA editing enzymes into mice (5).
The article by Gregory Koblentz (2) offers several practical and proactive steps that could help prevent the tragic misuse of synthetic biology technology. The proposed measures include limiting the capacity to perform certain types of research, requiring investigators to obtain synthetic DNA from approved vendors and extending special efforts to include private sector and citizen scientist communities as responsible partners in ensuring biosecurity and biosafety. One of the challenges is that persons with a wide range of educational backgrounds and work experiences enter what might be loosely termed the biotechnology field. This may pose a particular challenge when it comes to awareness of ethics issues. The U.S. National Institutes of Health mandated that all funded investigators with projects involving human research subjects complete online training courses to become familiar with the history and issues involved in the ethical conduct of such efforts. This might serve as a useful model for proactive outreach efforts to acquaint biotech workers with the fundamentals of biosecurity and best practices to ensure safety.
The remarkable pace of new biotechnology developments will necessitate continuous evaluation to detect emerging hazards. Perhaps the convergence of factors that will convey enormous power over life heralds a new age of wonders that will propel humans to the hypothetical H+ singularity. Unless we manage these technologies wisely, that singularity might end up being a vanishing point.
(1) Andrew Pollack. Traces of Terror: The Science; Scientists Create a Live Polio Virus. The New York Times, 12 July 2002. http://www.nytimes.com/2002/07/12/us/traces-of-terror-the-science-scientists-create-a-live-polio-virus.html
(2) Gregory D. Koblentz. Smallpox Could Again Be a Serious Threat. Slate, 19 October 2017. http://www.slate.com/articles/technology/future_tense/2017/10/synthetic_biology_could_lead_to_the_re_emergence_of_smallpox.html?wpsrc=sh_all_dt_tw_top
(3) David Baltimore et al. A Prudent Path Forward for Genomic Engineering and Germline Gene Modification. Science 348(6230):36-38. http://science.sciencemag.org/content/348/6230/36.full
(4) Jef D. Boeke et al. The Genome Project –Write. Science 353(6295):126-127. http://science.sciencemag.org/content/353/6295/126.full
(5) Heidi Ledford. CRISPR, the Disruptor. Nature, 3 June 2015. http://www.nature.com/news/crispr-the-disruptor-1.17673