Griffith, who was born at Hale in southern England, has been described variously as a “virtual recluse” or “quiet and retiring.” He worked as a bacteriologist at the Ministry of Health's pathology laboratory in London and was killed working in his laboratory during an air-raid.

Despite the general obscurity of his background Griffith has acquired long after his death a reputation as one of the founding fathers of molecular biology by his discovery in 1928 of bacterial transformation in pneumococci. He had first succeeded in distinguishing two types of pneumococci, the nonvirulent R (rough) of serological type I and the virulent S (smooth) of type III.

He inoculated mice with both live nonvirulent R and heat-killed S pneumococci. Although when either were inoculated separately no infection resulted, together they produced in the mice lethal cases of pneumonia. Further, he recovered from the infected mice living, virulent S pneumococci of type III.

It was this awkward result which later led Oswald Avery and his colleagues in 1944 to carry out the experiments that succeeded in explaining Griffith's results by suggesting that the power to transform bacteria lay with the nucleic acid of the cell rather than its proteins or sugars.