In 1928, bacteriologist Frederick Griffith worked on a vaccine for pneumonia, which is caused by Streptococcus pneumoniae bacteria. Griffith studied two pneumonia strains in mice: one pathogenic and one non-pathogenic. Only the pathogenic strain killed host mice.

Griffith made an unexpected discovery when he killed the pathogenic strain and mixed its remains with the live, non-pathogenic strain. Not only did the mixture kill host mice, but it also contained living pathogenic bacteria that produced pathogenic offspring. Griffith concluded that the non-pathogenic strain received something from the dead pathogenic strain that transformed it into the pathogenic strain; he called this the transforming principle.

At the time of Griffith’s studies, there was heated debate surrounding the identity of the genetic material. Much early evidence implicated proteins as the hereditary molecules. Griffith’s experiments on bacterial transformation provided some of the earliest data demonstrating that DNA is the genetic material.

Bacteria incorporate external DNA through transformation. Transformation occurs naturally but is also induced in laboratories—often to clone DNA. To clone a specific gene, scientists can insert the gene into a plasmid, a circular DNA molecule that can independently replicate. The plasmid often contains an antibiotic resistance gene. Bacteria take up the plasmid through transformation. Scientists then expose the bacteria to antibiotics. Surviving bacterial colonies should contain the plasmid because the plasmid contains an antibiotic resistance gene. DNA analysis can confirm the gene’s presence in the plasmid. Bacterial colonies with the desired gene propagate and can be used to make more plasmids or proteins.

Why would bacteria take in foreign DNA? Unlike sexually reproducing organisms, bacteria essentially clone themselves. This reproductive method, called binary fission, offers few opportunities for genetic variation. Although mutations introduce some diversity, many mutations are harmful. Sharing genes through transformation, as well as conjugation and transduction, allows prokaryotes to evolve.