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The Avery–MacLeod–McCarty experiment was an experimental demonstration, reported in 1944 by Oswald Avery, Colin MacLeod, and Maclyn McCarty, that DNA is the substance that causes bacterial transformation, in an era when it had been widely believed that it was proteins that served the function of carrying genetic information. It was the culmination of research in the 1930s and early 20th century at the Rockefeller Institute for Medical Research to purify and characterize the "transforming principle" responsible for the transformation phenomenon first described in Griffith's experiment of 1928: killed Streptococcus pneumoniae of the virulent strain type III-S, when injected along with living but non-virulent type II-R pneumococci, resulted in a deadly infection of type III-S pneumococci. In their paper "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", published in the February 1944 issue of the Journal of Experimental Medicine, Avery and his colleagues suggest that DNA, rather than protein as widely believed at the time, may be the hereditary material of bacteria, and could be analogous to genes and/or viruses in higher organisms.
With the development of serological typing, medical researchers were able to sort bacteria into different strains, or types. When a person or test animal is inoculated with a particular type, an immune response ensues, generating antibodies that react specifically with antigens on the bacteria. Blood serum containing the antibodies can then be extracted and applied to cultured bacteria. The antibodies will react with other bacteria of the same type as the original inoculation. Fred Neufeld, a German bacteriologist, had discovered the pneumococcal types and serological typing; until Frederick Griffith's studies bacteriologists believed that the types were fixed and unchangeable from one generation to the next.
Griffith's experiment, reported in 1928, identified that some "transforming principle" in pneumococcal bacteria could transform them from one type to another. Griffith, a British medical officer, had spent years applying serological typing to cases of pneumonia, a frequently fatal disease in the early 20th century. He found that multiple types—some virulent and some non-virulent—were often present over the course of a clinical case of pneumonia, and thought that one type might change into another. In testing that possibility, he found that transformation could occur when dead bacteria of a virulent type and live bacteria of a non-virulent type were both injected in mice: the mice would develop a fatal infection and die, and virulent bacteria could be isolated from such infected mice.
The findings of Griffith's experiment were soon confirmed, first by Fred Neufeld at the Koch Institute and by Martin Henry Dawson at the Rockefeller Institute. A series of Rockefeller Institute researchers continued to study transformation in the years that followed. With Richard H.P. Sia, Dawson developed a method of transforming bacteria in vitro. After Dawson's departure in 1930, James Alloway took up the attempt to extend Griffith's findings, resulting in the extraction of aqueous solutions of the transforming principle by 1933. Colin MacLeod worked to purify such solutions from 1934 to 1937, and the work was continued in 1940 and completed by Maclyn McCarty.