Making, Cloning, and the Expression of Human Insulin Genes in Bacteria: The Path to Humulin

Endocr Rev. 2021 May 25;42(3):374-380. doi: 10.1210/endrev/bnaa029.

Abstract

In the mid- to late 1970s, recombinant deoxyribonucleic acid methods for cloning and expressing genes in E. coli were under intense development. The important question had become: Can humans design and chemically synthesize novel genes that function in bacteria? This question was answered in 1978 and in 1979 with the successful expression in E. coli of 2 mammalian hormones, first somatostatin and then human insulin. The successful production of human insulin in bacteria provided, for the first time, a practical, scalable source of human insulin and resulted in the approval, in 1982, of human insulin for the treatment of diabetics. In this short review, I give my personal view of how the making, cloning, and expressing of human insulin genes was accomplished by a team of scientists led by Keiichi Itakura, Herbert W. Boyer, and myself.

Keywords: biotechnology; chemical DNA synthesis; genentech; recombinant DNA.

MeSH terms

  • Cloning, Molecular
  • DNA, Recombinant / metabolism
  • Escherichia coli* / genetics
  • Escherichia coli* / metabolism
  • Humans
  • Insulin / genetics
  • Insulin / metabolism
  • Insulin, Regular, Human* / genetics
  • Insulin, Regular, Human* / metabolism

Substances

  • DNA, Recombinant
  • Insulin
  • Insulin, Regular, Human