306 H. FRAENKEL-CONRAT AND B. SINGER 



and chemical aspects of TMV-RNA. In regard to its biological role, no new 

 unpublished findings can be reported. I will therefore only briefly review what 

 has previously been ascertained. Since the nucleic acid alone can cause infection 

 leading to the formation of progeny virus, it is obvious that it contains all the 

 necessary information for both its own replication and that of the protein with 

 which it is normally associated. When mixed viruses were prepared, containing 

 protein from one and nucleic acid from another strain of TMV, the symptoms of 

 the disease were indistinguishable from those provoked by the nucleic acid alone, 

 and by the original strain supplying the nucleic acid. Comparative analyses of 

 the composition of the corresponding progeny proteins has revealed no signi- 

 ficant and consistent differences. Although this question is still under investi- 

 gation, there is no question that the infection caused by nucleic acid of a certain 

 strain produces progeny protein very similar to that originally associated with 

 this nucleic acid, and quite different from the protein from a different strain 

 with which the nucleic acid may have been coated with prior to application. 



Having thus failed to produce mutants at will by the mixture of protein and 

 nucleic acid from different strains, otlier possible means to attain this end have 

 been investigated. The only indications of partial success have been observed 

 when the nucleic acids from two strains were mixed and then, with addition of 

 protein, transformed into reconstituted virus. Many of the virus lesions pro- 

 duced by this material behaved as if they were predominantly or completely 

 due to one strain, others appeared mixed, but lost their mixed character upon 

 further propagation. In two instances, however, new and stable mutants were 

 isolated from such mixtures which differed in disease symptoms and/or amino 

 acid composition from the two parent strains. Since a stable mutant has also 

 been observed upon propagation of a single nucleic acid, the two mutants iso- 

 lated from progeny obtained with mixed nucleic acids may be accidental and 

 not due to a fusion of the genetic material. Apart from the possible production 

 of mutants, these experiments should also throw Ught on another question which 

 has concerned us at the begiiming of this lecture, namely the size of the infectious 

 particle. For if we get an appreciable number of mixed lesions, this would be an 

 indication that nucleic acid preparations contain small, and yet active, nucleic 

 acid subunits, while predominantly pure lesions would favour the alternate 

 concept that only the intact nucleic acid cores were infectious. Unfortimately, 

 here as elsewhere in life and in chemistry, purity is difficult to establish or to 

 measure, and therefore the solution to this problem, as so many others which I 

 have mentioned, has to await the outcome of further experiments. 



REFERENCES 



1. H. Fraenkel-Conrat, J. Amer. ehem. Soc, 78, 882, 1956. 



2. A. Gierer & G. Schramm, Z. Naturf., iib, 138, 1956. 



3. H. Fraenkel-Conrat, B. Singer & R. C. Williams, in The Chemical Basis of 



Heredity, Ed. by W. D. McElroy and B. Glass), McCollum Pratt Symp. Johns Hop- 

 kins Press, Baltimore, p. 501, 1957. 



4. H. Fraenkel-Conrat, B. Singer & R. C. Williams, Biochim. biophys. Acta., 25, 



87j 1957- 



5. H. Fraenkel-Conrat, Ann. N. Y. Acad. Sei., in press. 



6. H. Fraenkel-Conrat & R. C. Williams, Proe. nat. Acad. Sei., Wash., 41, 690, 1955. 



7. A. Gierer, Nature, Land., 179, 1299, 1957. 



