Federation of American Scientists Case Studies in Dual Use Biological Research Module 2.0: Poliovirus Case Study
Topic: De Novo Synthesis of Poliovirus Subtopic: Poliovirus from Scratch

In 2001, Dr. Wimmer, Distinguished Professor in the Department of Molecular Genetics and Microbiology at the State University of New York (SUNY) at Stony Brook, stirred world-wide controversy when he announced that his lab had assembled synthetic poliovirus in a test tube without a DNA or RNA template, or the help of living cells. The efforts were a natural progression from earlier work conducted by his lab, which in 1991 published the chemical formula of poliovirus.

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In this publication, the authors professed their opinion that a virus is more analogous to a chemical than a living entity. Ten years later, Eckard Wimmer reported that his lab had chemically synthesized poliovirus according to its genomic sequence in the absence of a template. This experiment represented a scientific first: the assembly of a virus from scratch. To accomplish the synthesis, Dr. Wimmers lab deliberately used widely available, simple, but perhaps crude, methods to synthesize full-length poliovirus cDNA from the publicly available sequence. They started to assemble complete copies of the 7741 base pair virus by stringing together customized oligonucleotides (averaging 69 nucleotides each) which were bought from a commercial supplier. The process was time consuming, but straight-forward.

Once they had assembled the full-length cDNA, they transcribed it with RNA polymerase to make the single stranded RNA genome of poliovirus. Next, they made live virus by incubating the RNA in an extract from Hela cells. When injected into mice, the animals developed a neurological disease both chemically and histologically indistinguishable from poliomyelitis. Therefore, the authors concluded that they had indeed created a synthetic copy of poliovirus from scratch. This result for the first time demonstrated the feasibility of biochemically synthesizing an infectious agent in the absence of a template.


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