A reappraisal of the contribution of Friedrich Loeffler to the development of the modern concept of virus.

Abstract

Most virology textbooks, with the exception of the Afterword of A. J. Levine’s chapter in the third edition of Field’s Virology (1996), emphasize the contribution of Martinus Beijerinck (1898) to the birth of the modern concept of virus and they refer to Friedrich Loeffler (1898) only because he was the first to have shown the filterability of the animal virus Foot and mouth disease virus. Following Adolf Mayer [9] who first described the mosaic disease of tobacco and demonstrated that the sap of diseased tobacco plants was infectious, Dimitri Ivanowsky (1896) showed that such saps remained infectious after filtering through Chamberland filters. Beijerinck confirmed Ivanowsky’s observations and further showed that the infectious agent could diffuse through several millimeters of an agar gel, from which he concluded that the agent could not be a bacteria. Beijerinck also showed that the infectivity of sap remained constant during serial infections of plants, providing evidence that the agent could not be a toxin, since it was able to replicate itself in living organisms. The relative contributions of Mayer, Ivanowsky and Beijerinck have been extensively discussed by Bos [2]. Beijerinck was the first to use the term virus for such an infectious agent. He was, however, convinced that the agent was a liquid (or a solute: mentioned p. 6, line 16, in his 1898 article). In the title of his article he therefore named it: contagium vivum fluidum, or contagious living liquid. Beijerinck thought his interpretation was confirmed by the observation that the sap filtered through Chamberland candles was less infectious than unfiltered sap. He explained this reduction as resulting from adsorption of the agent to the surface of the filter, mainly at the beginning of the filtration. In a control experiment he found that the less diffusible (granulase) of two enzymes present in malt extracts was more strongly retained in Chamberland filters than the more diffusible enzyme (maltase), until saturation was reached. In a footnote of his 1898 paper (see Appendix I) he stated that he could not agree with Loeffler’s conclusion that the agent of foot-and-mouth disease was a particle and not a liquid. Friedrich Loeffler and Paul Frosch had been appointed in 1886 by the Government in Berlin to investigate the cause of foot-and-mouth disease and to find a way to protect cattle against the disease. The conclusions of the investigating Committee are described in two articles published a few months before the appearence of Beijerinck’s paper (Reports 1, 2 and 3: Loeffler and Frosch, 1898; Report 4: Loeffler, 1898; this latter article was cited by