Transformation

The first report of transformation was an example of natural transformation. Dr. Frederick Griffith was a public health microbiologist studying bacterial pneumonia during the 1920s. He discovered that when he first isolated bacteria from the lungs of animals with pneumonia, the bacterial colonies that grew on the agar plates were of reasonable size and had a glistening, mucoid appearance. When he transferred these colonies repeatedly from one agar plate to another, however, mutant colonies would appear that were much smaller and were chalky in appearance. He designated the original strains as "smooth" strains, and the mutants as "rough" strains. When Griffith injected mice with smooth strains they contracted pneumonia, and smooth strains of the bacterium could be reisolated from the infected mice. However, when he infected the mice with rough strains they did not develop the disease. The smooth strains were capable of causing disease, or were "virulent," while the rough strains did not cause disease, or were "aviruluent."

Griffith questioned whether the ability to cause disease was a direct result of whatever product was making the bacterial colonies smooth, or whether rough strains of the bacterium were less capable of establishing disease for some other reason. To investigate this idea, he prepared cultures of both bacterial types. He pasteurized (killed) each of these cultures by heating them for an hour and then injected the heat-treated extracts into mice. His hypothesis was that if the bacteria had to be living to cause disease, heat-treating that killed the bacteria would prevent disease. If, on the other hand, the smooth material was itself a toxin, heating would not destroy it, meaning heated extracts of smooth strains would continue to cause disease. When Griffith injected heated extracts of both smooth and rough strains into mice, neither caused disease. This suggested to him that only living smooth cells could cause disease.

In his next experiment he coinjected unheated, live rough bacteria with heat-treated, dead smooth bacteria into mice. All of the mice developed disease, and when bacteria were isolated from the lungs of the diseased mice, all the isolates were smooth. This led Griffith to propose that there was some "transforming principle" in the heated smooth extract that converted the rough strains back to smooth ones capable of causing diseases. Griffith was not able to determine the nature of this transforming principle, but his experiments suggested that some "inheritable" material present in the heated extract could genetically convert strains from one colony type to another.

Approximately ten years later, another research team, that of Oswald Avery, Colin Munro MacLeod, and Maclyn McCarty, followed up on Griffith's experiments by enzymatically and biochemically characterizing the heated transforming extracts that Griffith had produced. Their studies indicated that the transforming principle was deoxyribonucleic acid (DNA), providing the first definitive evidence that DNA was the inheritable material.