This is the story of how recombinant DNA was used to make a product that was chemically identical to human insulin. In the process, the industry of biotechnology was born. This story covers the origin of the premier biotech company, Genentech, as well as the invention of the insulin analogs like Humalog and Levemir.
☠️NONE OF THE INFORMATION IN THIS VIDEO SHOULD BE USED AS MEDICAL ADVICE OR OPINION. IT IS FOR GENERAL EDUCATION AND ENTERTAINMENT☠️
🎬C R E D I T S🎬
Written, performed, and edited by Patrick Kelly
Select imagery/video supplied by Getty Images
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📜 S O U R C E S 📜
Genentech: The Beginnings of Biotech (2011) by Sally Smith Hughes (not an affiliate link) https://press.uchicago.edu/ucp/books/book/chicago/G/bo8169877.html
Sally Smith Hughes oral history transcripts: https://oac.cdlib.org/view?docId=kt9c6006s1&brand=oac4&doc.view=entire_text
The Drug Hunters (affiliate link) https://amzn.to/3SCfoDP
Insulin: The Crooked Timber (affiliate link) https://amzn.to/4e06tns
Novo Nordisk by Kurt Jacobsen (2023)
Early Recombinant Protein Therapeutics (2017) https://application.wiley-vch.de/books/sample/3527340866_c01.pdf
The Evolution of Insulin and How it Informs Therapy and Treatment Choices (2020) https://academic.oup.com/edrv/article/41/5/733/5836295
Evolution of Insulin Delivery Devices: From Syringes, Pens, and Pumps to DIY Artificial Pancreas (2020) https://pmc.ncbi.nlm.nih.gov/articles/PMC7261311/
Insulin Lispro (2024) https://www.ncbi.nlm.nih.gov/books/NBK507840/
The Evolution of Insulin Glargine and its Continuing Contribution to Diabetes Care (2014) https://pmc.ncbi.nlm.nih.gov/articles/PMC4045187/
The Evolution of Insulin and How it Informs Therapy and Treatment Choices (2020) https://pmc.ncbi.nlm.nih.gov/articles/PMC7366348/
The insulin market reaches 100 https://pmc.ncbi.nlm.nih.gov/articles/PMC8915140/
DNA cloning: A personal view after 40 years (Cohen, 2013) https://pmc.ncbi.nlm.nih.gov/articles/PMC3785787/
Complementary DNA / Copy DNA definitions https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/complementary-dna
Human insulin vs animal insulin Cochrane Review (2005) https://pmc.ncbi.nlm.nih.gov/articles/PMC8406912/
Insulin Analogs https://dtc.ucsf.edu/types-of-diabetes/type2/treatment-of-type-2-diabetes/medications-and-therapies/type-2-insulin-rx/types-of-insulin/insulin-analogs/
The insulin dilemma in resource-limited countries. A way forward? (2010) https://link.springer.com/article/10.1007/s00125-010-1897-3
Human insulin from recombinant DNA technology (1983) https://www.jstor.org/stable/1690508
Papers Referenced
(1972) Berg paper https://pmc.ncbi.nlm.nih.gov/articles/PMC389671/
(1972) Cleavage of DNA by R1 Restriction Endonuclease Generates Cohesive Ends https://pmc.ncbi.nlm.nih.gov/articles/PMC389773/
(1972) DNA Nucleotide Sequence Restricted by the RI Endonuclease https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC389791&blobtype=pdf
(1973) Construction of Biologically Functional Bacterial Plasmids In Vitro https://pmc.ncbi.nlm.nih.gov/articles/PMC427208/
(1974) Replication and Transcription of Eukaryotic DNA in Escherichia coli https://www.pnas.org/doi/pdf/10.1073/pnas.71.5.1743
(1977) City of Hope expresses somatostatin https://www.science.org/doi/10.1126/science.412251
(1978/1979) CREATION OF HUMAN INSULIN https://www.pnas.org/doi/pdf/10.1073/pnas.76.1.106
(1980) HUMAN INSULIN PRODUCED BY RECOMBINANT DNA TECHNOLOGY: SAFETY AND HYPOGLYCÆMIC POTENCY IN HEALTHY MEN https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(80)90443-2/fulltext
(1982) BIOSYNTHETIC HUMAN INSULIN IN THE TREATMENT OF DIABETES: A Double-blind Crossover Trial in Established Diabetic Patients https://www.sciencedirect.com/science/article/abs/pii/S0140673682905487
⌛T I M E S T A M P S ⌛
0:00 intro
0:56 The origin of recombinant DNA
9:56 The birth of Genentech
19:50 The origin of insulin analogs
27:30 Lessons learned
#historyofmedicine #medicalhistory