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| Historic Instrument of the Month—Wendell M. Stanley’s Tobacco Mosaic Virus Crystals |
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| By Joseph Luna | ||
| October 2011 | ||
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Of all the artifacts in the historic instrument collection, one stands out as not being an instrument at all, but a reagent—a bit of white crystalline powder in a non-descript bottle. At first glance, this would appear wholly unremarkable, unless you happened to add a solution of this reagent to tobacco plants. In due time you would observe a mottled discoloration on the plants’ leaves that remarkably appeared to be transmissible from plant to plant, even after filtering out everything smaller than the smallest bacterium. Quite simply, you would have reconstituted an infectious agent known as Tobacco mosaic virus (TMV), incidentally the first virus discovered over a century ago. But a virus as a chemical? A century ago, this question was all the more perplexing, as viruses had only recently been discovered. What became the first known virus, TMV was first isolated by Russian biologist Dmitri Ivonovsky in 1892, but first recognized as a new infectious agent by Dutch microbiologist Martinus Beijernick in 1898.1 Beijernick is known as the father of virology for this observation, having correctly deduced that the infectious agent was neither a bacterium nor a toxin (which could be diluted out), but instead a “virus” which he framed as a soluble and living germ (contagium vivum fluidum). The same year, Freidrich Loeffler and Paul Frosch discovered the first animal virus as the causative agent in foot-and-mouth disease of cattle.2 Within a short time, a number of important human infectious diseases were found to be viral and not bacterial in origin, first with yellow fever in 1900 and polio shortly thereafter. Even maligned bacteria were susceptible to viral infections from “phages” discovered by Twort and d’Herrelle in 1915-17. Viruses were everywhere it seemed. Throughout this time, it was largely presumed from a microbiological perspective, on the basis of their ability to replicate as obligate parasites, that viruses were alive (in fact many viewed them as super-tiny bacteria). But from a chemical perspective, it soon became clear that many viruses were no larger or more complex than a few protein molecules, and thus considered too small to contain all the necessary metabolic components required of an authentic living organism. A cell, in any form it was argued, a virus was not. So the question quickly became rather simple, but incredibly profound: are viruses alive, or not? As with most interesting scientific questions, many arguments were put forth for both sides, but the central problem was one of purity. The main criterion for the presence of a virus then (and now) was whether the agent was filterable as mentioned previously. But how could one be absolutely sure that no bacteria (or any living cell) made it through the filter? The microbiologists were inclined to be convinced of a virus’ filterability by repeated and varied experimentations. The chemically inclined however, were not fully convinced. If a virus could be thought of chemically, then perhaps it could be purified and analyzed via chemical methods, and still tested on its host to ensure that it was still virulent. In the early 1930s, Rockefeller biochemist Wendell M. Stanley at the Institute’s Deptartment of Plant and Animal Pathology in Princeton set out to do just that. TMV had been crystallized around the time he started, but was found to be inactive, that is no longer infectious. Stanley worked out a procedure to crystallize the virus while retaining its infectivity; an important feat, since it proved that a virus could be isolated in a purely inanimate form.3,4 It was for these crystals now found in our bottle, that Stanley was awarded the 1946 Nobel Prize in Chemistry. As much as it was an intellectual triumph, this discovery is also notable for having been incorrectly interpreted. Stanley was convinced from his experiments that the virus crystals he isolated were composed entirely of proteins and replicated by auto-catalysis (not unlike a prion in many respects). In this manner, his interpretation overemphasized the inanimate nature of viruses as completely distinct though very much “dead” replication machines. He did not anticipate that a nucleic acid held the secret of a virus’ ability to replicate, following evolutionary principles that govern all living organisms (TMV is a positive sense single stranded RNA virus). Still, this discovery helped cement viruses as occupying a unique boundary between living and non-living. That is, inside a cell, few would doubt a virus’ animated, seemingly deliberate, and often deadly purpose. Outside a cell, however, a virus is about as dead as any other chemical, like the one that sits in a display case at the base of Caspary, dormant for over 50 years, with the vibrant potential to continually transform the living. References: |
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