Eli Lilly prepares for production of recombinant insulin

Ulrich was the first to clone human preproinsulin, but an earlier announcement had been made by Genetech that the insulin gene had been cloned.  The proinsulin gene product undergoes processing inside the cell.  The single linear chain of aminoacids is cleaved in two places, resulting in three different chains, called the A chain, B chain, and C chain.  The C chain is released separately by the cell (it is thought to have some physiological function in the body, but it is not clear what that function is).  The A and B chains are linked in two places by disulfide bonds, forming the insulin that is secreted into the blood stream.

Genentech had in 1978 artificially constructed DNA that would encode the A chain and the B chain of insulin.  They inserted these two pieces into E. Coli, so that they had two different strains of E. Coli that could produce the A and B chains separately. These two chains could then be combined into insulin, but it was not cost effective to do that.  The engineers at Eli Lilly preferred to work with proinsulin and convert it to insulin, a process they had 50 years of experience with.

After Ullrich had cloned the human proinsulin gene, Eli Lilly started preparing for production.  Eli Lilly built a 40,000 gallon tank, a fermentor, in which they could grow E Coli. That’s about 15 feet in diameter and 30 feet tall.  Two fermentors were built, one in England and on in Indianapolis, after Eli Lilly debated various locations.  One concern was geographic diversity.  Eli Lilly was concerned that a nuclear war could obliterate its operations in Indianapolis, the England plant could take over.