Ch.4 — The Pharmaceutical Industry • 65 
\ow they can also be mamit'actured by fermen- 
tation using genetically designed bacteria, as 
has been demonstrated by the production of in- 
sulin and human grow tb hormone. 
I\SI Ll\ 
Insulin, is composed of tw o chains— -\ and B— 
of amino acids. It is initially produced as a 
single, long chain called pre-|)i'oinsulin, which is 
cut into a shorter chain, proinsulin. Proinsulin, 
in turn, is cut into the ,\ anti B chains w hen a 
piece is cleav ed from the middle. (See figure 22.) 
\\ ork on the genetic engineering of insulin has 
pi'oceeded quickly. ,-\ year after one group re- 
ported that the insulin gene had been incorpo- 
I’ated into E. coli without e.xpression, a second 
group managed to grow colonies of £. coli that 
actually e.xcreted rat [)roinsulin. Then, within a 
couple of months, workers at (Jenentech, in col- 
laboration with a grouf) at City of Hope Medical 
Center, announced the se|)arate synthesis of the 
.\ (2 1 .\,-\) anti B (30 .A, A) chains of human insulin. 
The synthesis of the 1)N,A secjuences depended 
on advances in organic chemisti’v as well as in 
genetics. Six months were required simply to 
synthesize the necessary building blocks. 
Figure 22.— The Amino Acid Sequence of Proinsulin 
Connecting peptide 
A chain 
B chain 
Proinsulin is composed of 84 amino acid residues. When the connecting peptide is removed, 
the remaining A and B chains form the insulin molecule. The A chain contains 21 amino acids; 
the B chain contains 30 amino acids. 
SOURCE: Office of Technology Assessment. 
