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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 [18 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-pg18.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:	TRANSFORMATION OF PNI?UMOCOCCAL TYPES glutinated by the antiserum in the medium.šttempts to induce transforma- tion in suspensions of resting cells held under conditions inhibiting growth and multiplication have thus far proved unsuccessful, and it seems probable that transformation occurs only during active reproduction of the cells.¢mportant in this connection is the fact that the R cells, as well as those that have under- gone transformation, presumably also all other variants and types of pneu- mococci, contain an intracellular enzyme which is released during autolysis and in the free state is capable of rapidly and completely- destroying the activity of the transforming agent.¢t would appear, therefore, that during the loga- rithmic phase of growth when cell division is most active and autolysis least apparent, the cultural conditions are optimal for the maintenance of the balance between maximal reactivity of the R cell and minimal destruction of the trans- forming agent through the release of autolysic ferments. In the present state of knowledge any interpretation of the mechanism in- volved in transformation must of necessity be purely theoretical. The bio- chemical events underlying the phenomenon suggest that the transforming principle interacts with the R cell giving rise to a coordinated series of enzymatic reactions that culminate in the synthesis of the Type III capsular antigen. The experimental findings have clearly demonstrated that the induced altera- tions are not random changes but are predictable, always corresponding in type specificity to that of the encapsulated cells from which the transforming substance was isolated. Once transformation has occurred, the newly acquired characteristics are thereafter transmitted in series through innumerable trans- fers in artificial media without any further addition of the transforming agent. Moreover, from the transformed cells themselves, a substance of identical activity can again be recovered in amounts far in excess of that originally added to induce the change.¢t is evident, therefore, that not only is the capsular material reproduced in successive generations but that the primary factor, which controls the occurrence and specificity of capsular development, is also reduplicated in the daughter cells. The induced changes are not temporary modifications but are permanent alterations which persist provided the cul- tural conditions are favorable for the maintenance of capsule formation.­he transformed cells can be readily distinguished from the parent R forms not alone by serological reactions but by the presence of a newly formed and visible capsule which is the immunological unit of type specificity and the accessory structure essential in determining the infective capacity of the microorganism in the animal body. It is particularly significant in the case of pneumococci that the experi- mentally induced alterations are definitely correlated with the development of a new morphological structure and the consequent acquisition of new antigenic and invasive properties. Equally if not more significant is the fact that these changes are predictable, type-specific, and heritable.