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Avery, McLeod & McCarty Demonstrate that DNA is Responsible for Bacterial Transformation


In 1944 Canadian-born American physician and researcher Oswald T. Avery, Canadian-American geneticist Colin M. McLeod, and American geneticist Maclyn McCarty, at the Rockefeller Institute in New york, published "Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types. Induction of Transformation by a Desoxyribonucleic [sic] Acid Fraction Isolated from Pneumococcus Type III," Journal of Experimental Medicine 79 (1944) 137-58. The results reported in this paper demonstrated that DNA is the material responsible for bacterial  transformation.

In 1928 English bacteriologist Frederick Griffith demonstrated that Streptococcus pneumoniae, implicated in many cases of lobar pneumonia, could transform from one strain into a different strain. This phenomenon he attributed to an unidentified transforming principle or transforming factor.  In the years that followed a series of Rockefeller researchers, including Oswald Avery, continued to study transformation.

"Though interrupted, sometimes for years at a time, these studies were from 1928 onwards the centerpiece of Avery's lab agenda. Around 1940, they were activated by Colin MacLeod's efforts to purify the chemical agent responsible for changes of serotype — whether proteinnucleic acid, or some other class of molecule — and demonstrate that it was necessary and sufficient to cause the Griffith phenomenon. Studies on pneumococcal transformation were grossly burdened by a wide variety of variables, which needed to be controlled to allow quantitative estimation of transforming activity in extracts undergoing various stages of purification. MacLeod, over a number of years of research, had resolved several thorny technical issues to render the experimental system somewhat more reliable as an assay for biological activity. By the time McCarty arrived at the Rockefeller University, Avery's team had just about decided that the active reagent was not a protein. But what was it then? Could it be a soluble saccharide, RNA, or, least likely, DNA? The progress of this research over the next three years is beautifully described in McCarty's memoirThe Transforming Principle, written in the early 1980s.

"As purification progressed, exposure of extracts to crystalline RNase and to proteinase preparations helped Avery's team determine that the biological activity of extracts was not dependent on RNA or protein. Crystalline DNase was not available until 1948, but biological activity was rapidly reduced by tissue extracts rich in DNase. McCarty's arrival at Rockefeller University was also marked by another milestone, namely, the development of a diphenylamine reagent assay to positively correlate DNA with biological activity. It gradually became evident that the active material in purified extracts had astonishingly high potency in micrograms of DNA that could consummate the pneumococcal transformation in vitro.

"McCarty, MacLeod, and Avery wrestled with the standard of proof required to claim that they had accomplished pneumococcal transformation with highly purified DNA from extracts. After much self-inquiry, in 1944, they published in the Journal of Experimental Medicine that the active material was, indeed, DNA, bereft of protein or any other known polymer" (Wikipedia article on MacLyn McCarty, accessed 12-22-2013).

J. Norman (ed) Morton's Medical Bibliograhy 5th ed (1991) no. 255.3.

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