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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 [19 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-pg19.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‘55 Various hypotheses have been advanced in explanation of the nature of the changes induced. In his original description of the phenomenon Griffith (1) suggested that the dead bacteria in the inoculum might furnish some specific protein that serves as a "pabulum" and enables the R form to manufacture a capsular carbohydrate. More recently the phenomenon has been interpreted from a genetic point of view (26, 2J). The inducing substance has been likened to a gene, and the capsular antigen which is produced in response to it has been regarded as a gene product. In discussing the phenomenon of transformation Dobzhansky (2i) has stated that "If this transformation is described as a genetic mutation-and it is difficult to avoid so describing it-we are dealing with authentic cases of induction of specific mutations by specific treatments...... Another interpretation of the phenomenon has been suggested by Stanley (2S) who has drawn the analogy between the activity of the transforming agent and that of a virus. On the other hand, N'furphy (29) has compared the causa- tive agents of fowl tumors with the transforming principle of Pneumococcus. He has suggested that both these groups of agents be termed "transmissible mutagens" in order to differentiate them from the virus group. Whatever may prove to be the correct interpretation, these differences in viewpoint indi- cate the implications of the phenomenon of transformation in relation to similar problems in the fields of genetics, virology, and cancer research. It is, of course, possible that the biological activity of the substance described is not an inherent property of the nucleic acid but is clue to minute amounts of some other substance adsorbed to it or so intimately associated with it as to escape detection. If, however, the biologically active substance isolated in highly purified form as the sodium salt of desoxyribonucleic acid actually- proves to be the transforming principle, as the available evidence strongly- suggests, then nucleic acids of this type must be regarded not merely as structurally important but as functionally active in determining the biochemical activities and specific characteristics of pneumococcal cells. Assuming that the sodium desoxyribonucleate and the active principle are one and the same substance, then the transformation described represents a change that is chemically in duced and specifically directed by a known chemical compound.¢f the results of the present study on the chemical nature of the transforming principle are confirmed, then nucleic acids must be regarded as possessing biological specificity the chemical basis of which is as yet undetermined. SUMMARY 1. From Type III pneumococci a biologically active fraction has been isolated in highly purified form which in exceedingly minute amounts is capable under appropriate cultural conditions of inducing the transformation of unencapsu- lated R variants of Pneumococcus Type 11 into fully encapsulated cells of the