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The recombinant DNA (rDNA) technology initially appeared during the 1960- 1970s, even though the fundamental principle of recombination was revealed much earlier. In fact, in the year 1928, an English bacteriologist named Frederick Griffith who was researching about the bacteria responsible for an epidemic of pneumonia in London, first illustrated the genetic transformation. In his experiment, the living cells took up genetic material released by other cells and were transformed phenotypically by the new genetic information. More than ten years later, Oswald Avery recapitulated Griffith's experiment in which he isolated the transforming molecule later came to be known as DNA. These early investigations revealed that in the laboratory, DNA can be transferred from one cell to another and thus altering the original genetic phenotype of a life form.

The tradition of cutting, pasting, and copying the DNA can be traced back to Arthur Kornberg's successful replication of viral DNA (DNA polymerase). This was followed by the Werner Arber's breakthrough discovery of restriction enzymes in bacteria that degrade foreign viral DNA while protecting their own DNA. The discovery that ligase enzyme could be utilized to glue the DNA molecules together accelerated the rDNA technology research, popularly known as playing god in the history of humans.

Recombinant DNA (rDNA), also called as in vitro recombination, is a procedure concerned with creating and purifying the genes of interest. Gene cloning (molecular cloning) involves generating recombinant DNA and introducing it into a host cell that is replicated. One of the fundamental strategies of molecular cloning is to move genes of interest from a complex and large genome to simple, small one. The method of in vitro recombination makes it possible to cut different strands of DNA, outside the cell (in vitro), with the aid of a restriction endonuclease and link the DNA molecules together by means of complementary base pairing.