RDT Presentation On

STORY OF HUMAN INSULIN MASS PRODUCTION

Prepared By : BHUMIKA . R . SHARMA Roll No. : MBT/11/113 Class : MBA - BT

Insulin is not a cure for diabetes; it is a treatment. It enables the diabetic to burn sufficient carbohydrates, so that proteins and fats may be added to the diet in sufficient quantities to provide energy for the economic burdens of life.
Sir Frederick Grant Banting

History of Insulin Production

In 1921 the Canadian scientists Fredrick G. Banting, Charles H. Best,J.J.R. Macleod and James B. Collip discovered insulin, a peptide (small protein hormone) which lowers blood sugar. They extracted insulin from the islets of animal pancreases A year later, in January 1922, bovine insulin was first given to humans by injection Beginning in 1922, and in the face of great demand for the new medicine, several companies were granted licenses by the University of Toronto to manufacture insulin

In 1936, protamine, a low-weight protein, was used to develop a slow-release insulin

In 1950 yet another approach led to the presently available isophane NPH (neutral protamine Hagedorn) insulin, which is also bound to protamine

In 1951 the amorphous lente insulins (IZS) semilente, lente and ultralente were developed
In 1956, the first antidiabetic oral drugs sulfonamide (tolbutamide, carbutamide) and biguanide derivatives (metformin, phenformin) came on the market

History of Insulin Production

In 1974, chromatographic purification techniques allowed the production of highly purified animal insulin. This product was called monocomponent MC by Novo and single peak insulin by Eli Lilly In 1975, fully synthetic insulin (CGP 12 831) was synthesized in the laboratories of CibaGeigy in Basel In 1978, scientists from the biotechnology corporation Genentech in San Francisco, Calif., using a genetically manipulated plasmid of E. coli bacteria, succeeded in producing insulin with the same amino sequence as seen in humans

In 1980, recombinant DNA human insulin was first tested on 17 nondiabetic volunteers in England
The race to mass produce human insulin using gene technology was won by Eli Lilly in 1982 when the FDA approved Humulin R (rapid) and Humulin N (NPH) for the US market Since 1996, different insulin analogues have been introduced worldwide.These are characterized by various pharmacokinetics. Today, Humalog (Lilly), Lantus and Apidra (Aventis), Levemir and NovoRapid (Novo Nordisk) are available

Insulin - first recombinant protein to be produced

Insulin is an important hormone which regulates metabolism sugar

An inability to produce insulin results in a form of diabetes, this disease can be treated by daily injections of insulin Historically, insulin from pigs or cows is used, but known to produce immune reactions in some patients Challenge: how to make human insulin to be used as a drug in cell systems or microbes?

Insulin - first recombinant protein to be produced

Idea: take the gene of human insulin, clone into a plasmid, introduce the plasmid into E. coli or cells, and use them E.coli as Biological Factory for insulin production Amino acid sequence produced insulin (Contains 51 amino acids) and is identical to that of the natural human protein and it will not cause any immune reactions Much more economical than attempts to produce insulin by chemical synthesis

So, how to do this?

Strategy for insulin production

Harnessing the power of Recombinant DNA Technology - Human Insulin Production by Bacteria

Human Insulin Production by Bacteria

3
and cut with a restriction enzyme

6) join the plasmid and human fragment

Human Insulin Production by Bacteria

Mix the recombinant plasmid with bacteria.

Screening bacterial cells to learn which contain the human insulin gene is the hard part.

Route to the Production by Bacteria of Human Insulin

One cell with the recombinant plasmid

A fermentor used to grow recombinant bacteria. This is the step when gene cloning takes place The single recombinant plasmid replicates within a cell Then the single cell with many recombinant plasmids produces trillions of like cells with recombinant plasmid and the human insulin gene

Route to the Production by Bacteria of Human Insulin

The final steps are to collect the bacteria, break open the cells, and purify the insulin protein expressed from the recombinant human insulin gene.

Human Insulin in Market

Human Insulin in Market