The test‐tube synthesis of a chemical called poliovirus

Abstract

In July 2002, newspapers across the globe reported that scientists had created a virus in a test tube. This unexpected news struck a raw nerve among lay people and scientists alike. The work was condemned as dangerous and irresponsible, scorned as a stunt and perceived as a challenge to divine power. It was also hailed as a milestone in biology. What really happened? Guided by the nucleotide sequence, which my colleagues and I determined in 1981 (Kitamura et al , 1981), Jeronimo Cello, Aniko Paul and I described the chemical synthesis of a DNA molecule equivalent to the poliovirus genome (Cello et al , 2002). Using methods that we developed in the 1980s and 1990s (van der Werf et al , 1986; Molla et al , 1991), we then converted the virus‐specific DNA by simple in vitro biochemical manipulations into authentic poliovirus particles (Cello et al , 2002). On paper, the synthesis looked simple and, not surprisingly, it was immediately predicted—correctly—that a similar method could be used to synthesize any virus, including smallpox. Poliovirus, which was discovered nearly a century ago by Karl Landsteiner and Erwin Popper (1909), is a human virus that replicates in the gastrointestinal tract after ingestion. In rare instances, the virus invades the central nervous system where it destroys motor neurons that control muscle movement. This results in a terrifying disease, called poliomyelitis, which leads to irreversible paralysis and even death (Mueller et al , 2005a). Although the virus is relatively benign—the ratio of infection to neurological complication ranges from 1:100 to 1:1,000—the speed with which it spreads caused frightening epidemics among unprotected populations during the first half of the twentieth century. The development of two vaccines, the inactivated poliovirus vaccine (IPV) of Jonas Salk in 1954 and the attenuated oral vaccine (OPV) of Albert Sabin in 1957, broke the …