CHEMICAL STUDIES ON VIRUSES — STANLEY 361 



thought they were proteins ; others thought they were carbohydrate in 

 nature ; still other scientists thought they were lipid or fatlike ; and, 

 of course, the main discussion centered around the question whether 

 they were living organisms or nonliving entities. 



In order to resolve this chaotic situation it seemed desirable to at- 

 tempt to concentrate and purify one of the medium-sized viruses and 

 learn something about the nature of the purified material. At this 

 time no such virus had ever been obtained in pure form ; hence little 

 or nothing was known about the physical and chemical properties or 

 true nature of such a virus. Needless to say, these small viruses ap- 

 peared to be very mysterious, although today it is exceedingly difficult 

 to appreciate the early aura of mystery which surrounded them. The 

 virus selected for study was the one that was discovered first, namely, 

 tobacco mosaic virus. Extracts of plants diseased with this virus were 

 subjected to the ordinary methods of protein chemistry, and in 1935 

 it was found that an unusual material, which could be obtained in the 

 form of long, needlelike crystals, seen in plate 1, figure 1, could be 

 isolated from these extracts. 



This material was soon found to be a nucleoprotein having a particle 

 or molecular w^eight far greater than that of any known protein, 

 namely, of the order of 50 million. When solutions containing only 1 

 part per billion of this material were applied to normal tobacco plants, 

 it was found that these plants came down with the tobacco mosaic 

 disease, and from these plants additional quantities of this same un- 

 usual crystallizable nucleoprotein could be obtained. This material 

 was not present in extracts of normal plants. The same material was 

 also obtained from otlier kinds of plants diseased with tobacco mosaic, 

 and it seemed probable that this material represented the infectious 

 agent or virus. However, because of the fact that viruses had been 

 generally regarded as living organisms, there was a persistent tend- 

 ency to doubt that this crystallizable nucleoprotein actually repre- 

 sented tobacco mosaic virus. There were many suggestions that this 

 material was merely a pathological nucleoprotein associated wdth the 

 disease and that the true infectious agent or virus had not been isolated. 



Fortunately, methods were gradually developed by means of which 

 it was possible to correlate a given virus activity with a given physical 

 entity, and, by means of a series of such correlation experiments, re- 

 sults have been obtained in the case of tobacco mosaic virus which 

 permit the conclusion that, beyond a reasonable doubt, the crystal- 

 lizable nucleoprotein rod, 15 m/x by 300 m,u in size, actually is tobacco 

 mosaic virus. During the past 19 years no experimental data incon- 

 sistent with this conclusion have been obtained. This result indicates 

 that a single molecule can carry within its own structure all that is 

 necessary to predetermine reproduction or to cause replication and 



