Microbiological research is increasingly troubled by ethical questions regarding its potential misuse. In the near future, a criminal, terrorist, or state seeking to build a bioweapon might choose to obtain a pathogen by synthesizing it in vitro and changing its properties, instead of isolating it from nature or stealing it from maximum-containment facilities. Numerous logistical and technological obstacles complicate the construction and release of a bioweapon, but the first step–obtaining a suitable agent through clandestine synthesis–is becoming a realistic scenario that needs to be addressed by scientists and the arms control community.
In the past, in-vitro synthesis of biological agents was restricted to viruses with small infectious genomes that not only had to be sequenced fully but also had to be physically available as templates. In 2002, researchers at SUNY Stony Brook first demonstrated that a template genome was not necessary to create a poliovirus from scratch. Over a two-year time period, this group assembled the genome using short overlapping oligonucleotides designed according to the published poliovirus genome sequence and ordered through a commercial supplier. Similar experiments in 2003 yielded an encephalomyocarditis virus.
The newest technology on the market, fittingly named gene synthesis, combines microfluidic chip technology, one-step polymerase chain reaction assembly, and a novel assembly technique to accurately create large nucleotide building blocks that can later be joined. By using these new techniques in combination with standard molecular biology, it will be feasible to synthesize genomes the size of all known viruses and bacteria in vitro.
Limiting access to the sequence information on which the design of genomes is based could control what is synthesized, but would the costs be worth the benefits? Addressing the following questions would help to understand this larger issue: