Avery–MacLeod–McCarty experiment
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.
When a person or test animal (e.g., a mouse) is inoculated with a particular type, an immune response ensues, generating antibodies that react specifically with antigens on the bacteria.
Griffith, a British medical officer, had spent years applying serological typing to cases of pneumonia, a frequently fatal disease in the early 20th century.
[8] 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.
To show that it was DNA rather than some small amount of RNA, protein, or some other cell component that was responsible for transformation, Avery and his colleagues used a number of biochemical tests.
[1] Follow-up work in response to criticism and challenges included the purification and crystallization, by Moses Kunitz in 1948, of a DNA depolymerase (deoxyribonuclease I), and precise work by Rollin Hotchkiss showing that virtually all the detected nitrogen in the purified DNA came from glycine, a breakdown product of the nucleotide base adenine, and that undetected protein contamination was at most 0.02% by Hotchkiss's estimation.
In particular, many of the geneticists known informally as the phage group, which would become influential in the new discipline of molecular biology in the 1950s, were dismissive of DNA as the genetic material (and were inclined to avoid the "messy" biochemical approaches of Avery and his colleagues).
[17] In 1946, however, Joshua Lederberg and Edward Tatum demonstrated bacterial conjugation in E. coli and showed that genetics could apply to bacteria, even if Avery's specific method of transformation was not general.
[21] Avery's work also motivated Maurice Wilkins to continue X-ray crystallographic studies of DNA, even as he faced pressure from funders to focus his research on whole cells, rather than biomolecules.
[17] Despite the significant number of citations to the paper and positive responses it received in the years following publication, Avery's work was largely neglected by much of the scientific community.
Despite the much less precise experimental results (they found a not-insignificant amount of protein entering the cells as well as DNA), the Hershey–Chase experiment was not subject to the same degree of challenge.
