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Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types: Induction of Transformation by a Desoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III. January 1944.

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Title:	Studies on the Chemical Nature of the Substance [17 of 23]
Alternative Title:	Induction of Transformation by a Desoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III
Creator:	Avery, Oswald T.
Contributor:	MacLeod, Colin M.
Publisher:	Journal of Experimental Medicine
Date:	1944-01-00
Subject:	Cellular signal transduction
Description:	From the Journal of Experimental Medicine Vol. 79, No. 1.
Type:	Text
Format:	text/plain
Language:	en
Identifier:	avery-pg17.jpg
Source:	Master scanned with Epson GT-10000+ flatbed scanner at 600 dpi.
Rights:	http://osulibrary.orst.edu/specialcollections/coll/pauling/dna/copyright.html
Full Text:	OSWALD T. AVERY, COLIN M. MAcLEOD, AND MACLYN McCARTY‘53 The techniques used in the study of transformation appear to afford a sensitive means of testing the validity of this hypothesis, and the results thus far ob- tained add supporting evidence in favor of this point of view. If it is ultimately proved beyond reasonable doubt that the transforming activity of the material described is actually an inherent property of the nucleic acid, one must still account on a chemical basis for the biological specificity of its action. At first glance, immunological methods would appear to offer the ideal means of determining the differential specificity of this group of biologically important substances. Although the constituent units and general pattern of the nucleic acid molecule have been defined, there is as yet relatively little known of the possible effect that subtle differences in molecular configuration may exert on the biological specificity of these substances. However, since nucleic acids free or combined with histories or protamines are not known to function antigenically, one would not anticipate that such differences would be revealed by immunological techniques.œonsequently, it is perhaps not sur- prising that highly purified and protein-free preparations of desoxyribonucleic acid, although extremely active in inducing transformation, showed only faint trace reactions in precipitin tests with potent Type III antipneumococcus rabbit sera. From these limited observations it would be unwise to draw any conclusion concerning the immunological significance of the nucleic acids until further knowledge on this phase of the problem is available. Recent observations by Lackman and his collaborators (25) have shown that nucleic acids of both the yeast and thymus type derived from hemolytic streptococci and from animal and plant sources precipitate with certain antipneumococcal sera.­he reac- tions varied with different lots of immune serum and occurred more frequently in antipneumococcal horse serum than in corresponding sera of immune rab- bits. The irregularity and broad cross reactions encountered led these in- vestigators to express some doubt as to the immunological significance of the results. Unless special immunochemical methods can be devised similar to those so successfully used in demonstrating the serological specificity of simple non-antigenic substances, it appears that the techniques employed in the study of transformation are the only ones available at present for testing possible differences in the biological behavior of nucleic acids. Admittedly there are many phases of the problem of transformation that require further study and many questions that remain unanswered largely because of technical difficulties. For example, it would be of interest to know the relation between rate of reAtion and concentration of the transforming substance; the proportion of cells transformed to those that remain unaffected in the reaction system.¡owever, from a bacteriological point of view, nu- merical estimations based on colony- counts might prove more misleading than enlightening because of the aggregation and sedimentation of the R cells ag-