British bacteriologist Frederick Griffith (1879–1941) was perhaps the first person to show that hereditary information could be transferred from one cell to another “horizontally” (between members of the same generation), rather than “vertically” (from parent to offspring). In 1928, he reported the first demonstration of bacterial transformation, a process in which external DNA is taken up by a cell, thereby changing its characteristics. He was working with two strains of Streptococcus pneumoniae, a bacterium that causes pneumonia: a rough (R) strain and a smooth (S) strain. The R strain is nonpathogenic and lacks a capsule on its outer surface; as a result, colonies from the R strain appear rough when grown on plates. The S strain is pathogenic and has a capsule outside its cell wall, allowing it to escape phagocytosis by the host immune system. The capsules cause colonies from the S strain to appear smooth when grown on plates.
In a series of experiments, Griffith analyzed the effects of live R, live S, and heat-killed S strains of S. pneumoniae on live mice. When mice were injected with the live S strain, the mice died. When he injected the mice with the live R strain or the heat-killed S strain, the mice survived. But when he injected the mice with a mixture of live R strain and heat-killed S strain, the mice died. Upon isolating the live bacteria from the dead mouse, he only recovered the S strain of bacteria. When he then injected this isolated S strain into fresh mice, the mice died. Griffith concluded that something had passed from the heat-killed S strain into the live R strain and “transformed” it into the pathogenic S strain; he called this the “transforming principle.” These experiments are now famously known as Griffith’s transformation experiments.
In 1944, Oswald Avery, Colin MacLeod, and Maclyn McCarty were interested in exploring Griffith’s transforming principle further. They isolated the S strain from infected dead mice, heat-killed it, and inactivated various components of the S extract, conducting a systematic elimination study. They used enzymes that specifically degraded proteins, RNA, and DNA and mixed the S extract with each of these individual enzymes. Then, they tested each extract/enzyme combination’s resulting ability to transform the R strain, as observed by the diffuse growth of the S strain in culture media and confirmed visually by growth on plates. They found that when DNA was degraded, the resulting mixture was no longer able to transform the R strain bacteria, whereas no other enzymatic treatment was able to prevent transformation. This led them to conclude that DNA was the transforming principle. Despite their results, many scientists did not accept their conclusion, instead believing that there were protein contaminants within their extracts.
Parker, N., Schneegurt, M., Thi Tu, A.-H., Forster, B. M., & Lister, P. (n.d.). Microbiology. Houston, Texas: OpenStax. Access for free at: https://openstax.org/details/books/microbiology