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November 28, 2001

Insulin

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Question from the United Kingdom:

How is artificial insulin made?

Answer:

What a great question! I’m not sure how much detail you’re interested in, but here is the short answer. Insulin is created in a special non-disease-producing laboratory strain of E. coli bacteria (not the same type that causes diarrhea and kidney problems that you may be familiar with) that has been genetically altered by the addition of the gene for human insulin production. The bacteria produces the insulin which is then chemically harvested from the medium in which the bacteria is grown, purified and prepared for human use.

Here is the long answer if you are interested: [Note: the following is adapted from Overview of Biotechnology at the End of the 20th Century. Please see that reference for even more details.]
Modern biotechnology began when recombinant human insulin was first marketed in the United States in 1982. The effort leading up to this landmark event began in the early 1970’s when research scientists developed protocols to construct vectors, by cutting out and pasting pieces of DNA together to create a new piece of DNA (recombinant DNA), that could be inserted into the bacterium, Escherichia coli (transformation). If one of the pieces of the new DNA included a gene which produced a protein enzyme that broke down a particular antibiotic, the bacterium would be resistant to that antibiotic and could grow in a medium containing it. To the piece of DNA that conferred resistance of Escherichia coli to a particular antibiotic was added the human gene for the making of insulin. If this recombinant DNA containing the human insulin gene was used to transform Escherichia coli,and the bacteria were plated on an agar plate containing the antibiotic, the bacteria that grew contained not only the antibiotic resistant gene but also the insulin gene. Additional new pieces of DNA were then added to promote the expression of the human insulin gene so that this new recombinant DNA (expression vector) could be used to transform Escherichia coli. Thus, large quantities of human insulin messenger RNA were formed, which in turn were translated into large quantities of the human insulin protein which could then be harvested from the medium in which the transformed Escherichia coli was grown. This insulin could then be marketed as the human derived insulin that is on the market today. Various types of insulin (Regular, NPH, Ultralente, Lente, Glargine etc. could be made by changing the DNA vector which was inserted into the E. coli bacteria or modifying the insulin once it was produced. This would change the structure of the insulin protein molecule which would result in longer or shorter acting insulins.

MSB