Prior to the use of recombinant DNA technology to modify bacteria to produce human growth hormone, the hormone was manufactured by extraction from the pituitary glands of cadavers, as animal growth hormones have no therapeutic value in humans. Production of a single year's supply of human growth hormone required up to fifty pituitary glands[3], creating significant shortages of the hormone.[4] In 1979, scientists at Genentech produced human growth hormone by inserting DNA coding for human growth hormone into a plasmid that was implanted in escherichia coli bacteria. The gene that was inserted into the plasmid was created by reverse transcription of the mRNA found in pituitary glands to complementary DNA. HaeIII, a type of restriction enzyme which acts at restriction sites "in the 3' noncoding region"[5] and at the 23rd codon in complementary DNA for human growth hormone, was used to produce "a DNA fragment of 551 base pairs which includes coding sequences for amino acids 24–191 of HGH."[5] Then "a chemically synthesized DNA 'adaptor' fragment containing an ATG initiation codon..."[5] was produced with the codons for the first through 23rd amino acids in human growth hormone. The "two DNA fragments... [were] combined to form a synthetic-natural 'hybrid' gene."[5] The use of entirely synthetic methods of DNA production to produce a gene that would be translated to human growth hormone in escherichia coli would have been exceedingly laborious due to the significant length of the amino acid sequence in human growth hormone. However, if the cDNA reverse transcribed from the mRNA for human growth hormone were inserted directly into the plasmid inserted into the escherichia coli, the bacteria would translate regions of the gene that are not translated in humans, thereby producing a "pre-hormone containing an extra 26 amino acids"[5] which might be difficult to remove.
