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Transformation does not always require a viral vector; it can be done using chemical treatments or electroporation.
Ref: NCERT Class 12 Biology Chapter 9: Biotechnology: Principles and Processes Competent Host and Gene Transfer Methods
Oswald Avery, Colin MacLeod, and Maclyn McCarty in 1944 purified transforming principle from heat-killed S pneumococci. They sequentially removed lipids, polysaccharides, and proteins with enzymes, showing activity remained after protease and RNase treatments but was abolished by deoxyribonuclease. Chemical analysis revealed DNA with high viscosity, phosphorus content, and diphenylamine reaction positive. Transformation of rough to smooth required intact DNA, proving DNA rather than protein carries genetic specificity. This milestone established DNA as genetic material preceding Hershey-Chase confirmation and transformed molecular biology understanding.
Ref: Avery et al., Journal of Experimental Medicine 1944: Studies on Chemical Nature of Transforming Principle; Hartl, Chapter 1
Griffith chose Streptococcus pneumoniae, then called pneumococcus, diplococcus causing lobar pneumonia, because it exhibited two colony morphologies linked to virulence. Smooth colonies produce thick polysaccharide capsule preventing phagocytosis, virulent. Rough colonies lack capsule due to mutation in capsule biosynthesis enzymes, avirulent. Capsule antigens defined serotypes II and III used in cross-transformation tests. This organism was amenable to mouse infection model and grew on simple media. Its natural competence later made it ideal for transformation studies by Avery and for discovery of DNA as genetic material.
Ref: NCBI Bookshelf, Streptococcus pneumoniae Biology; Avery et al., Journal of Experimental Medicine 1944: Model Organism
Frederick Griffith in 1928 mixed heat-killed virulent smooth S Streptococcus pneumoniae bearing polysaccharide capsule with live avirulent rough R noncapsulated strain and injected into mice. R alone was harmless, but mixture killed mice and yielded live S recovered from blood. Heat-stable substance from dead S transformed R genotype to S, acquiring capsule genes and virulence heritably. This phenomenon was named transformation, first demonstration bacteria exchange genetic traits. Later Avery identified material as DNA, but Griffith established principle of horizontal genetic information transfer.
Ref: Griffiths et al., Introduction to Genetic Analysis, Chapter 1: Griffith Experiment; Nature: Classic Transformation
